Nikoghosyan et al. BMC Cancer 2010, 10:607 http://www.biomedcentral.com/1471-2407/10/607 S T U D Y P R O T O C O L Open Access Randomised trial of proton vs. carbon ion radiation therapy in patients with chordoma of the skull base, clinical phase III study HIT-1-Study Anna V Nikoghosyan1*, Irini Karapanagiotou-Schenkel2, Marc W Münter1, Alexandra D Jensen1, Stephanie E Combs1, Jürgen Debus1 Abstract Background: Chordomas of the skull base are relative rare lesions of the bones. Surgical resection is the primary treatment standard, though complete resection is nearly impossible due to close proximity to critical and hence also dose limiting organs for radiation therapy. Level of recurrence after surgery alone is comparatively high, so adjuvant radiation therapy is very important for the improvement of local control rates. Proton therapy is the gold standard in the treatment of skull base chordomas. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors. Methods/design: This clinical study is a prospective randomised phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie centre (HIT) and is a monocentric study. Patients with skull base chordoma will be randomised to either proton or carbon ion radiation therapy. As a stan- dard, patients will undergo non-invasive, rigid immobilization and target volume delineation will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment (acceler- ated dose) will be 63 Gy E ± 5% and 72 Gy E ± 5% (standard dose) in proton therapy respectively. Local-progres- sion free survival (LPFS) will be analysed as primary end point. Toxicity and overall survival are the secondary end points. Additional examined parameters are patterns of recurrence, prognostic factors and plan quality analysis. Discussion: Up until now it was impossible to compare two different particle therapies, i.e. protons and carbon ions directly at the same facility. The aim of this study is to find out, whether the biological advantages of carbon ion therapy can also be clinically confirmed and translated into the better local control rates in the treatment of skull base chordomas. Trial registration: ClinicalTrials.gov identifier: NCT01182779 Background Chordomas (1 - 4% of all malignant bone tumors) of the skull base are relative rare lesions of the bones. The incidence is around 100 new cases per year in Germany and 0.08/100000 in the US corresponding to around 300 new cases per year [1]. Chordomas arise from embryo- nic remnants of the notochord and are found at the base of the skull area in 35% of all cases. According to the histopathological findings, chordomas are divided * Correspondence: anna.nikoghosyan@med.uni-heidelberg.de 1Dept. of Clinical Radiology, University of Heidelberg, INF 400, 69120 Heidelberg, Germany Full list of author information is available at the end of the article into conventional (most common), chondroid and dedif- ferentiated types [2,3]. Histological differentiation between chordomas and chondrosarcomas is difficult and must contain immunhistochemical tests [4]. Chor- doma is immunopositive for epithelial markers like cyto- keratin and endothelial membrane antigen (EMA), whereas chondrosarcoma is negative for both. Both chordomas and chondrosarcomas can be positive for S- 100 and vimentin. The average age at the diagnosis is 49 years for base of skull localization. Also, the base of the skull is the most common localisation of chordomas in children and adolescents. In children and adolescents chordomas © 2010 Nikoghosyan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.