Phase I/II Therapy Trial to Determine the Safety and Efficacy of Heavy Ion Radiotherapy in Patients With Osteosarcoma
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents.
For effective treatment, local control of the tumor is absolutely critical, because the
chances of long term survival are <10% and might effectively approach zero if a complete
surgical resection of the tumor is not possible. Up to date there is no curative treatment
protocol for patients with non-resectable osteosarcomas, who are excluded from current
osteosarcoma trials , e.g. EURAMOS1. Local photon radiotherapy has previously been used in
small series and in an uncontrolled, highly individualized fashion, which, however,
documented that high dose radiotherapy can, in principle, be used to achieve local control.
Generally the radiation dose that is necessary for a curative approach can hardly be
achieved with conventional photon radiotherapy in patients with non-resectable tumors that
are usually located near radiosensitive critical organs such as the brain, the spine or the
pelvis. In these cases Heavy Ion Radiotherapy (HIT) may offer a promising new alternative.
Moreover, compared with photons, heavy ion particles provide a higher physical selectivity
because of their finite depth coverage in tissue. They achieve a higher relative biological
effectiveness. Phase I/II dose escalation studies of HIT in adults with non-resectable bone
and soft tissue sarcomas have already shown favorable results.
Methods/Design: This is a monocenter, non-randomized study for patients older than 6 years
of age with non-resectable osteosarcoma. Desired target dose is 60-66 Cobalt Gray Equivalent
(GyE). Weekly fractionation of 6 x 3 Gy E is used. HIT will be administered exclusively at
the Ion Radiotherapy Center in Heidelberg. Furthermore, FDG-PET imaging characteristics of
non-resectable osteosarcoma before and after HIT will be investigated prospectively.
Systemic disease before and after HIT is targeted by standard chemotherapy protocols and is
not part of this trial.
The primary objectives of this trial are the determination of feasibility and toxicity of
HIT. Secondary endpoints are tumor response, disease free survival and overall survival. The
aim is to improve outcome for patients with non-resectable osteosarcoma.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
feasibility, toxicity (tox) measured by the CTC Criteria .Unacceptable:grade 4 tox. A rate of acute tox (≤ 3 months during/after RT) > grade 3 of ≤ 5% and a rate of late tox > grade 3 of ≤ 3% will be acceptable.
before, weekly during RT and at follow-up (1, 6 and 19 weeks, 6, 12, 24, 36 48 and 60 months after RT).
Juergen Debus, Head of Dep.
Heidelberger Ionenstrahltherapiezentrum, HIT, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Germany: Federal Office for Radiation Protection