Carbon Ion Radiotherapy in Germany: Update on the Clinical Results from 394 patients Treated at the University of Heidelberg and on the Future Perspectives at the Heidelberg Ion Therapy Center (HIT)

Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 23, 2008

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Presenter: Stephanie e. Combs
Presenter's Affiliation: University of Heidelberg
Type of Session: Scientific

Background

Chordomas (C) are rare, slow growing tumors which are thought to arise from remnants of the notochord. Though slow growing, they can be locally aggressive and tend to involve the axial skeleton, often involving the base of skull. Chondrosarcomas (CS) are malignant cartilaginous tumors which account for approximately 6% of base of skull tumors. 

 
Adenoid cystic carcinomas (ACC) tumors can arise from the major or minor salivary glands and can be locally aggressive with late local or distant recurrences. There is often perineural invasion with ACC. ACC have a poor outcome and new treatment modalities are needed to improve local control, particularly in patients with partially resected disease, particularly in ACC which involve the base of skull. 
 
Surgical resection is generally done initially for debulking and to obtain a diagnosis. Complete resection is preferable; however, due the critical structures in the base of skull, this is often difficult. As there is often residual disease post operative radiation therapy is frequently used.  Due to the involvement of the base of skull, it can be difficult to get adequate dose to the tumor while still sparing critical normal structures such as the brainstem, optic nerves and chiasm. Photon therapy has not resulted in good local control rates in C or CS. Charged particle therapies may improve local control rates due to their greater conformality, which may allow higher doses of radiation to be delivered safely. 
 
Carbon ion therapy has been available since 1997 in Germany. The present study presents the results for patients treated with carbon ion therapy at Gesellschaft fur Schwerionenforschung (GSI).

Materials and Methods

A total of 407 patients have been treated with carbon ion radiotherapy at GSI as of the latest analysis, with the majority of patients being treated for CS and C of the base of skull, ACC and sacral chordomas. Data was collected prospectively. The data presented today focused on a Phase I/II trial of Carbon ion beam therapy for CS and a second Phase I/II trial of C treated with carbon ion beam.

 
Patients were treated stereotactically using a mask fixation system. All patients had CT and MRI imaging performed for target delineation. Daily imaging with orthogonal X-rays was performed. Biological plan optimization was done using Trip software which is based on the local effect model (LEM) which was developed by Scholz et al. at GSI. Carbon ion therapy was delivered using a raster scanning technique. Both C and CS of the base of skull were treated to a median dose of 60 cobalt Gray equivalents (CGE) in 20 fractions. Patients were treated seven days a week in 3 CGE fractions. Sacral chordomas were treated with IMRT with carbon ion therapy used as a boost to a dose of 18 CGE in six fractions. Adenoid cystic carcinomas with base of skull invasion were also treated with IMRT with a carbon ion boost to 18 CGE in six fractions.   

Results

CS:

A total of 54 patients were accrued from 1998-2001. The median age of patients was 46 years and the majority had grade I or II tumor (~65%).   Local Control (LC) was 96.2% at three years and 89.8 at four years. Overall survival (OS) was 98.2% at 5 years. 
 
C:
Patients were accrued from 1998-2001. LC was 80.6% at three years and 70% at 5 years. OS was 88.5% at five years. The authors found improved LC with doses greater than 60 CGE.
 
When compared with prior studies the median dose for C and CS of the base of skull treated with carbon ions was higher and this resulted in higher LC rates compared with photon based radiation. 
 
ACC:
LC was 77.5% at 2 years and remained 77.5% at 4 years when combined treatment with photon radiation with a carbon ion boost was used as compared with 72.2% at 2 years and 24.6% when photons alone were used. 

Author's Conclusions

1)      Carbon ion treatment is clinically feasible and safe.
2)      Carbon ion therapy provides excellent LC rates which are superior to those seen with photon radiation alone.
3)       Patients are currently being accrued for a phase I/II trial evaluating the efficacy and safety of a carbon ion boost used in conjunction with photon radiation in intermediate risk prostate cancer patients. 
4)      The GSI facility can treat approximately 70 patients a year with carbon ion therapy and the new HIT facility which is to resume clinical operation in 2008 can treat an additional 1,300 patients a year.          

Clinical/Scientific Implications

Carbon ions have several possible advantages in treating tumors which are in close proximity of critical structures, such as tumors of the base of skull. The lateral penumbra as well as the Bragg peak of carbon ion beams are sharper than protons beams and this may allow greater conformality. This conformality may allow even greater sparing of critical normal structures and allow dose escalation which may improve local control. 

 
The relative biological effect (RBE) of carbon ions is also higher (~3) than protons or photons however, it does change with depth, energy and tissue, which complicates treatment planning. The concurrent used of chemotherapy and biological agents with carbon ions also requires further study to determine if there may be a greater combined effect compared with multimodality proton/photon therapy.
 
The present study suggests that carbon ion therapy is safe and effective in the treatment of cancers of the base of skull and may improve local control. Prior to broader adoption of this modality, further studies are needed to determine the efficacy of this modality (in part due to its immense cost) and the late effects of carbon ion therapy on normal tissues. 



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