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20 years of tumor therapy: Clinical studies began in 1998


Twenty years ago, researchers at GSI Helmholtzzentrum für Schwerionenforschung began to conduct clinical studies of an innovative cancer treatment that used accelerated carbon ions. In August and September 1998, the first patients were treated with a complete course of carbon therapy for a period of three weeks. It was a starting point of a success story that has led from fundamental research to a widespread medical application.

The therapy was the result of joint research by the GSI Helmholtzzentrum, the Clinic of Radiology and the German Cancer Research Center (DKFZ) in Heidelberg, and the Helmholtz research laboratory in Rossendorf. Individual radiation treatment with heavy ions had initially been conducted as early as December 1997. This had been preceded by four years of technical development of the therapy unit at the heavy-ion accelerator of GSI, which included a radiation facility for patients, and by 20 years of fundamental research in radiation biology and physics.

Treatment with ion beams is a very precise and highly effective, yet extremely gentle, therapeutic process. The major advantage of this method is that the ion beams, which have previously been brought to very high speeds in the accelerator facility of GSI, develop their strongest effect in the tumor itself, while sparing the healthy tissue that surrounds it. Because the range of the heavy-ion beam can be controlled with millimeter precision, particles are stopped inside the tumor and can release their energy there in a concentrated burst. As a result, this process is especially suited for deep-seated tumors that are located near high-risk organs such as the optic nerve or the brain stem.

The raster-scan method, which was also developed at GSI and was used in heavy-ion therapy for the first time, enables the carbon beam to cover the tumor very precisely. The radiation dose can be applied to the malignant tumor tissue point by point. In order to regulate the intensity of the effect, the beam is left long enough at each point to reach the intended dose. Despite the large number of dots/pixels, the irradiation of a field takes only a few minutes. This process makes it possible to irradiate very precisely tumors with complex shapes, and it is a great improvement over conventional beam delivery methods.

In the period until 2008, GSI used carbon ion beams to treat more than 440 patients for tumors of the head and neck with great success. Today, special clinics in Heidelberg (Heidelberg Ion-Beam Therapy Center — HIT) and Marburg (Marburger Ionenstrahl-Therapiezentrum — MIT) and Shanghai, China, offer customized versions of the treatment that was first used at GSI in Darmstadt 20 years ago. The initiator and the crucial pioneer of this tumor therapy is Professor Gerhard Kraft, who created GSI’s biophysical research department in the early 1980s and was its director from 1981 to 2008. This is how he remembers the early years: “Back then, most people would hardly have thought it possible to make the outstanding biomedical properties of ion beams technically available for therapy. That became possible only through the collaboration of many disciplines, such as nuclear and atomic physics, radiation biology and radiation medicine, accelerator physics, computer science, to name just a few.”

The Scientific Managing Director of GSI and FAIR, Professor Paolo Giubellino, emphasizes the great social benefits of this treatment: “This method is an outstanding example of how fundamental research benefits society and individual patients through successful technology transfer, and how it is being continuously advanced today.” The establishment of the facilities in Heidelberg and Marburg — in whose development and construction GSI played a major role — by no means marks the end of the research work in this field. Additional medical applications are also a major goal of the biophysical research that will be conducted in the APPA program, which is one of the four major research pillars of the future accelerator center FAIR that is currently being built at GSI. FAIR can offer new research opportunities for the next-generation particle therapy, for example using very high-energy ions for radiography or radioactive ions for PET imaging online.

“Having pioneered heavy ion therapy in Europe, GSI is now the main center for research in this field” says the successor of Professor Kraft as Director of the Biophysics Department, Professor Marco Durante. “We are committed to improve particle therapy for the benefit of the patients, and to seek new strategies and solutions to use heavy ion beams for treating cancer and noncancer diseases”, concludes Durante. For example, scientists in the Biophysics Department are working on the combination of heavy ion therapy and immunotherapy. They are also investigating the use of ion beams to treat cardiac arrhythmia. Here too, the advantages of ion therapy — extremely precise point-by-point application and optimal protection of the surrounding tissue — can be put to good use. As a result, in the next few years carbon ions could be successfully used to treat cardiac arrhythmia as a noninvasive alternative to the present treatment with cardiac catheters or drugs.

Another major goal is to treat moving tumors in the inner organs, such as is the case with lung, liver and pancreatic cancer. The ion beam is targeted very exactly, and for this reason the patients must be held in place with millimeter precision so that this high-precision radiation can be effective. However, tumors in the abdominal and thoracic cavities are moved by the patient’s breathing and heartbeat. Current research is therefore searching for ways to achieve the precision and homogeneity that ion beam radiation requires in order to treat moving targets as well as fixed ones. Tumor therapy with heavy ions thus still offers great opportunities for further scientific findings that will enable it to be used even more effectively in the future for the benefit of many patients. (BP)

Treatment Facility at GSI
Raster scan method
Application in clinical operation
The photo shows the treatment space at the GSI accelerator, where the clinical studies on tumor therapy with heavy ions were conducted. To ensure precise irradiation of the tumor the head of the patient has to be secured in a mask individually produced for each patient.
The tumor is divided into layers. The depth of a layer is adjusted by varying the energy of the carbon ions. Magnetic deflectors scan the beam from left to right as well as up and down on each layer.
At the Heidelberg Ion Beam Therapy Centre HIT, the tumor therapy with heavy ions developed at GSI is implemented in routine operation.
Photo: A. Zschau/GSI
Picture: GSI Helmholtzzentrum für Schwerionenforschung GmbH
Photo: Mathias Ernet, Springer Medizin