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 Nikoghosyan,Alexandra D Jensen,Jürgen Debus,Stephanie E Combs,Marc W Münter,Irini Karapanagiotou-Schenkel

doi:10.1186/1471-2407-10-607

Abstract

BackgroundChordomas 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/designThis 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 standard, 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 (accelerated dose) will be 63 Gy E ± 5% and 72 Gy E ± 5% (standard dose) in proton therapy respectively. Local-progression 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.DiscussionUp 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 registrationClinicalTrials.gov identifier: NCT01182779

Highlights

Chordomas of the skull base are relative rare lesions of the bones
The aim of this study is to find out, whether the biological advantages of carbon ion therapy can be clinically confirmed and translated into the better local control rates in the treatment of skull base chordomas
Primary objectives/endpoints of the study The primary objective of this study is to evaluate, if the innovative therapy in chordomas is superior to the standard proton treatment with respect to the Local-progression free survival (LPFS) defined as time from the randomisation to observed local recurrence or death from any cause in the absence of documented local disease progression

Summary

Introduction

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 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. Chordomas (1 - 4% of all malignant bone tumors) of the skull base are relative rare lesions of the bones. The base of the skull is the most common localisation of chordomas in children and adolescents. In children and adolescents chordomas may behave more aggressively [5].

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