ESTRO 38 Abstract book

S129 ESTRO 38

proton therapy centres there is a need for international cooperation and consensus in developing appropriate QA procedures. The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG) is a multi-professional group with Clinicians, Physicists and RTTs collaborating to address this issue by learning from what has already been done for early trials and working together to find solutions to the unaddressed challenges. However, the centres also need confidence in their delivery from day one and other groups such as the European Particle Therapy Network (EPTN) are developing surveys and audits which can help to set the standards required for the implementation of practice-changing trials. Simultaneously, there is a need for calibration procedures which are specific to PT. Primary standards laboratories are working with clinical centres to develop calibration protocols and procedures which are straightforward to use whilst creating minimal uncertainty in the complete dosimetry chain. The aim will be to bring these endeavours together to determine which QA is important for PT clinical trials and how it impacts on clinical outcomes. Longer term this will create confidence that the trial outcomes reflect differences in randomisation schedules rather than variations in accuracy of treatment delivery across different centres. An additional benefit of comprehensive trials QA is the impact on the general standard of treatment delivered. SP-0262 Limitations of current RBE models and their implication for clinical trial design N. Matsufuji 1 1 National Institute of Radiological Sciences NIRS, Department for Accelerator and Medical Physics, Chiba, Japan Abstract text Unlike conventional X-ray, changing radiation quality within irradiation field and resultant enhancing relative biological effectiveness (RBE) toward its range end makes ion-beam therapy advantageous in realizing intense clinical effect on the deep-seated target while sparing surrounding normal tissues. On another front, this changing RBE of the ion beam makes it indispensable to use an appropriate RBE model that bridges between the radiation quality as input and biological effectiveness as output for safe and efficient ion-beam therapy. In Japan, the first RBE model dedicated for carbon-ion radiotherapy (CIRT) was established in a pragmatic manner, i.e. , dose distribution was at first designed from in-vitro cell survival response of a reference human salivary gland (HSG) cell as a verifiable biological endpoint, then it was scaled to meet clinical response for therapeutic purpose. Recently the model was updated by integrating the microdosimetric kinetic model (MKM) that realizes to estimate the biological effectiveness of any radiation accurately from its microdosimetric therefore measurable quantity while the indication of the RBE-weighted therapeutic dose has been inherited. At National Institute of Radiological Sciences (NIRS), clinical trials of CIRT have been conducted with the RBE model since 1994 for various solid tumors. More than 11,000 patients have been treated in the past 24 years, and the retrospective analysis of the derived clinical outcomes have revealed the appropriateness of the RBE model. At the same time, there is still certain room for future improvement in the ongoing RBE model especially for coming biologically adaptive therapy. Among possible biological factors, current model explicitly considers only the radiosensitivity of one HSG cells. The tumor-specific difference in response is treated just as the difference in optimum dose found in the dose-escalation clinical trials. In addition, heterogeneity of the tumor such as variation in O 2 pressure or the existence of radioresistant stem cells are not considered yet. The response of surrounding normal

tissues has been analyzed recently, however, further study is necessary to take them into consideration in the treatment planning. In the world, different approach has been adopted in European facilities. Local Effect Model (LEM), another biological model developed at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Germany, shows almost comparable performance with MKM as model itself, however, different biological endpoint and reference condition selected for therapeutic application results in different indication of the therapeutic RBE-weighted dose even though the same physical dose is delivered. The difference in RBE between the models needs careful translation of the therapeutic RBE-weighted dose from one to the other. For instance, in the international clinical trial for pancreatic cancer treatment CHIPHER (Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer), 57.6 Gy (RBE) will be prescribed in total for those to be treated in Japanese CIRT facilities while 59.4 Gy (RBE) will be given for those placed to European facilities to deliver the identical absorbed dose. Translation of the tolerance dose of organs-at-risk (OARs) between the models is further complex therefore not yet achieved, however, add further weight in international clinical trials ahead. SP-0263 Clinical trials on carbon ion radiotherapy for locally advanced pancreatic cancer. T. Ohno 1 1 Gunma University, Gunma University Heavy Ion Medical Center, Maebashi, Japan Abstract text Carbon ion radiotherapy (C-ion RT) offers excellent dose distribution, enabling a concentrated administration of a sufficient dose within a target volume while minimizing the dose in the surrounding normal tissues. Additionally, C-ion RT provides biological advantages not seen in proton or photon therapy, owing to high linear energy transfer (LET); C-ion RT induces increased double-stranded DNA structures, causing irreversible cell damage independently of cell cycle phase or oxygenation, more so than lower LET irradiation such as proton and photon therapy. C-ion RT has been in use for more than 20 years in Japan and the efficacy and safety of this therapy, especially for photon- resistant tumors such as bone and soft tissue sarcoma, non-squamous cell carcinomas of the head and neck, pancreatic cancer, and rectal cancer is well accepted. For locally advanced unresectable pancreatic cancer, a phase I/II clinical study was conducted and recommended schedule of the combination of carbon ion radiotherapy (55.2 Gy (RBE) in 12 fractions for 3 weeks) and gemcitabine (1000 mg/m 2 /weekly) was determined. Subsequently operated C-ion RT centers have used the schedule. Recent multicenter retrospective clinical study demonstrated that the reproducible clinical efficacy was observed. The 2-year overall survival was 60% for patients treated with 55.2 Gy (RBE) in 12 fractions concurrent with chemotherapy. Based on these backgrounds, multicenter randomized clinical study on locally advanced pancreatic cancer comparing carbon ion radiotherapy with IMRT was conducted. In my talk, rationale, accumulated clinical outcomes, and future perspectives of C-ion RT for pancreatic cancer will be presented.

Proffered Papers: RB 3: Tumour sensitization

OC-0264 CDK4/CDK6 inhibition radiosensitises HPV-neg HNSCC through inhibition of homologous recombination E. Gottgens 1 , K. Leszczynska 2 , J. Bussink 1 , E. Hammond 2 , P. Span 1 1 UMC St Radboud Nijmegen, Department of Radiation Oncology, Nijmegen, The Netherlands; 2 CRUK-MRC