ESTRO 38 Abstract book

S308 ESTRO 38

The real time knowledge of 10 B concentration in tumour is crucial to exploit BNCT selectivity. Aim of the present work is the efficiency evaluation of a theranostic agent for MRI guided BNCT. Material and Methods The theranostic agent, developed at Torino University, consists of a carborane cage (10 atoms of boron) bound on one side to a Low Density Lipoprotein (LDL) used to target tumour cells, and a Gd 3+ complex on the other for the detection of the agent through Magnetic Resonance Imaging (MRI). The expression of LDLs transporters is upregulated in many tumours and here is exploited to reach the 10 B selective uptake. The theranostic agent was tested in different murine tumour models including: B16 skin melanoma, Her2+ breast tumour, ZL34 and AE17 malignant pleural mesothelioma. EML4-ALK transgenic mouse model was used as primary lung tumour. The in vitro and in vivo studies of selective accumulation and 10 B quantification were carried out at Torino University, while the thermal neutron irradiation was designed and performed at the TRIGA Mark II research nuclear reactor of Pavia University. Results The in vitro studies showed the tumour selective uptake of the theranostic agent and led to the identification of the optimum post injection time to realise BNCT. Three groups of animals for each models were considered: the cold control group, the neutron irradiated group (without 10 B administration) and the BNCT treated group. The animals were followed up for 20 up to 40 days after irradiation and in all the experiments the BNCT treated groups showed a significant reduction in tumour growth with respect to the control groups. Conclusion A theranostic agent for MRI guided BNCT was developed and positively applied in preclinical treatment of small animal tumour models. The possible use of this kind of boronated agents in clinical BNCT will improve BNCT outcomes making possible the personalisation of the treatment on the 10 B accumulation response of each single patient. OC-0588 Combing hyperthermia and/or OXi4503 with low LET radiation is equivalent to high LET radiation alone P.B. Elming 1 , B.S. Sørensen 1 , H. Spejlborg 2 , J. Overgaard 1 , M.R. Horsman 1 1 Aarhus University Hospital, Dept. of Experimental Clinical Oncology, Aarhus, Denmark ; 2 Aarhus University Hospital, Dept. Oncology, Aarhus, Denmark Purpose or Objective Tumor hypoxia is a major factor causing resistance to low linear energy transfer (LET) radiation (i.e., photons). One solution to this problem is to use high LET radiation (i.e., carbon ions), but such an approach is not so readily accessible. However, additional therapies increase the efficacy of low LET radiation and may make tumor response equivalent to that seen with high LET radiation. We investigated this by combining low LET radiation with hyperthermia and/or the vascular disrupting agent (VDA) OXi4503. Material and Methods A C3H mammary carcinoma, implanted in the right rear foot of CDF1 mice, was used for all experiments when at 200 mm 3 in size. Treatments were performed on restrained, non-anaesthetised, animals with the tumor bearing leg exposed and immersed in a water bath maintained at 25 O C for radiation (240 kV X-rays) alone or with heating at 41-43 O C for 60 minutes. Radiation was applied either in the middle of the heating period (simultaneous treatment), or 1-hour (early sequential treatment) or 4-hours (late sequential treatment) prior to heating. OXi4503 (50 mg/kg) was intraperitoneally

injected 1.5 hours prior to irradiating. Tumor response was the percentage of mice showing local tumor control 90 days after treatment with graded radiation doses, and following logit analysis of the radiation dose-response curve, the TCD50 value (radiation dose causing tumor control in 50% of mice) was estimated. Results The TCD50 value for low LET photon irradiation alone was 54 Gy. Our previous studies with carbon ions in the same tumor model reported a TCD50 value that was 1.5 times lower than that seen with photons (Sørensen et al., Acta Oncol., 2015;54:1623-30). A similar enhancement ratio (ER; ratio of TCD50 values for radiation alone and radiation + modifier) of 1.5 was obtained with a temperature of 41.5 O C when administered simultaneously with the low LET radiation. For a late sequential radiation and heat treatment, temperatures of 42.5 O C and above were necessary, although an ER of 1.5 was observed at 41.5 O C if this sequential treatment was combined with OXi4503; the VDA alone gave an ER of around 1.3. The effect of using an early sequential approach is under investigation. Conclusion The local tumor control obtained with high LET carbon ions is also possible with low LET photons if combined with hyperthermia. However, the temperature at which this equivalent response is observed is dependent on the radiation and heat sequence, and whether a VDA is included in the treatment schedule. OC-0589 RBE-weighted dose in carbon ion therapy: impact of the RBE model translation on clinical outcomes S. Molinelli 1 , M. Bonora 2 , B. Vischioni 2 , J.E. Dale 3 , S. Russo 1 , S. Casale 4 , M.R. Fiore 2 , I. Fumagalli 5 , A. Hasegawa 6 , L. Preda 7 , P. Fossati 8 , F. Valvo 2 , M. Ciocca 1 1 National Center for Oncological Hadrontherapy, Medical Physics, Pavia, Italy; 2 National Center for Oncological Hadrontherapy, Clinical Department, Pavia, Italy; 3 Haukeland University Hospital, Department of Oncology and Medical Physics, Bergen, Norway ; 4 Institute of Radiology IRCCS San Matteo University Hospital, Department of Diagnostic Medicine, Pavia, Italy ; 5 University of Milano Bicocca, Faculty of Medicine, Milano, Italy ; 6 Osaka Heavy Ion Therapy Center, Clinical Department, Osaka, Japan; 7 National Center for Oncological Hadrontherapy, Radiology Department, Pavia, Italy ; 8 MedAustron, Clinical Department, Wiener Neustad, Austria Purpose or Objective With the aim of taking advantage of the long term experience in carbon ion radiotherapy (CIRT) of the National Institute of Radiological Sciences (NIRS), we implemented at the National Center for Oncological Hadrontherapy (CNAO) a conversion scheme for relative biological effectiveness (RBE)-weighted prescription doses (D RBE ) to account for the use of a different carbon ion RBE model (1). No correction was applied for NIRS defined constraints to optic pathways, brainstem and rectum, thus following a conservative approach. The purpose of this study is to assess the clinical implications of the described method on tumor control. Material and Methods Plans of 60 Adenoid Cystic Carcinoma (ACC) and 25 sacral chordoma (SC) patients, previously treated at CNAO with a Local Effect Model I (LEMI)-D RBE optimization, were exported for recalculation with a Microdosimetric Kinetic Model (MKM)-D RBE calculation system. The latter model is currently in use at NIRS . In addition, 10 patients treated at NIRS for a pancreatic lesion were used for RBE evaluation in this tumor site. LEMI prescription doses were 68.8 Gy(RBE) and 70.4 Gy(RBE) in 16 fractions and 57.6 Gy(RBE) in 12 fractions for the ACC, SC and pancreas cases, respectively. D RBE to 95%, 50% and 2% of the clinical