81: Adaptive radiotherapy for head & neck squamous cell carcinoma

S40 81 Adaptive radiotherapy for head & neck squamous cell carcinoma V. Gregoire Dept. of Radiation Oncology & Center for Molecular Imaging, Radiation & Oncology, Université catholique de Louvain, StLuc University Hospital, Brussels, Belgium In Radiation Oncology for Head and Neck tumors, conformal treatment with IMRT has been recently demonstrated to be the standard of care. However, target volumes (TV) and organs at risk (OAR) are typically delineated on pretreatment CT or MR images. This is obviously a simplification, as patient's external contours, TVs and to a lesser extent OARs will likely change during treatment. Tracking the reduction in TV during IMRT offers the prospect of a progressive cone down of the irradiated volume, thus leading to a progressive dose reduction in the non-target tissues with potential decrease in treatment morbidity. In addition, adaptive radiotherapy could also potentially allow for a dose increase to the tumor, thus potentially leading to better local control. A proof of concept study performed in our group in a series of HNSCC have shown that after a mean dose of 46 Gy (of 70 Gy) the primary tumor GTV assessed with CT and MR had substantially decreased leading to subsequent reduction of the high dose volume. A subsequent study has shown that the use of FDG-PET, which allows a more accurate delineation of the primary tumor GTV, could further reduce the high dose volume. Adaptive radiotherapy requires the use of a very strict methodology for image acquisition, image segmentation, and volume and dose registration. For volume segmentation of FDG-PET images, recent data have shown that gradient-based methods are more powerful to distinguish between residual tumor activity and peri-tumoral inflammation induced by treatments. It is likely that non-rigid methods will be required for registering the various sets of images acquired during treatments. Also, the summation of dose during treatment when deformation of anatomic structures is likely to affect the expected dose distribution, still remain an unresolved issue. Last, outcome research to demonstrate the clinical benefit of adaptive IMRT is presently lacking. During the lecture, the various issues of adaptive IMRT in Head and Neck tumors will be reviewed and illustrated with original data from the presenting author's group. 82 An example of the integrated model: the EORTC DAHANCA1219 trial V. Gregoire1, J. Overgaard2, E. Shash3 1 Dept. of Radiation Oncology & Center for Molecular Imaging, Radiation & Oncology, Université catholique de Louvain, St-Luc University Hospital, Brussels, Belgium 2 Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark 3 EORTC Data Center, Brussels, Belgium. Head and neck cancer is the 5th common malignancy worldwide, and among these tumors locally advanced squamous cell carcinoma of the head and neck (HNSCC) are the most frequent. The treatment of such locally advanced HNSCC is predominately radiotherapy, alone or combined with simultaneous chemotherapy. Several biological modifications of radiotherapy of HNSCC have markedly improved the outcome in form of both locoregional control, disease specific and overall survival. These modifications include the use of altered fractionation (i.e. accelerated and hyperfractionation), hypoxic modification and concomitant chemo-radiotherapy. Recently a 15-gene hypoxia classifier has been identified and tested retrospectively in 323 patients with head and neck carcinoma treated with radiotherapy and either placebo or nimorazole in the DAHANCA-5 protocol. The

ICTR-PHE – 2014 classifier has been demonstrated to be an efficient tool to categorize tumors for their hypoxic status and therefore responsiveness to combination treatment with radiation and hypoxic modifier. In this framework, DAHANCA and EORTC decided to join forces to conduct an international randomized trial aiming at evaluating in a blinded randomized trial, whether the hypoxic cell radiosensitizer nimorazole can improve the effect of primary curative accelerated fractionated concomitant chemo-radiotherapy with concomitant cisplatin given to patients with locally advanced HPV/p16 negative HNSCC. Patients will be stratified according to their gene signature of hypoxia to investigate if the hypoxic gene profile can predict which patient benefit from the use of hypoxic cell sensitizer.

Several translational research studies will be associated to this clinical trial aiming at identifying other molecular markers of radioresponsivenes, and at testing the use of hypoxic PET tracers for patient selection. 83 Evaluation of existing ripple filter designs for clinical use at the MedAustron ion beam therapy facility L. Grevillot, S. Vatnitsky EBG MedAustron GmbH, Wiener Neustadt, Austria Purpose: Ripple filter is commonly used in active scanning delivery systems at carbon ion beam therapy facilities. The main function of this device is to reduce the number of energy layers required to produce a homogeneous dose distribution in the target volume, by increasing the width of pristine Bragg peaks of carbon ions. The purpose of this study was to evaluate different ripple filter designs, focusing on their clinical implementation at MedAustron. Materials and methods: The existing ripple filter designs implemented at ion beam therapy centers have been reviewed. Preliminary Monte Carlo simulations based on the GATE/GEANT4 code have been performed for the selected ripple filter designs, in order to identify their performances. Further measurements have been conducted for a limited set of carbon ion energies, in order to verify the Monte Carlo investigations. Based on these measurements, a realistic Monte Carlo model of the beam delivery has been developed and used to extrapolate the ripple filter transfer function at any available energy. Results: Two ripple filter designs have been selected. The design of the ripple filters and the manufacturing process are dependent on carbon ion beam energy and are especially sensitive to low energy carbon ions. Monte Carlo simulation was found to be a very useful tool in the selection process. It allowed to prepare an effective test plan for the evaluation of the selected ripple filter prototypes with clinical beam and also to extrapolate the limited set of measurements to any type of foreseen clinical situation, without use of additional beam time.