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Clinical experience with proton therapy at PSI

Proton therapy is based on about fifty years extensive and positive experience of the effect of proton beams on diseased and healthy cells in the body. To date, about 100,000 patients have been treated with protons at more than 40 centers world-wide, predominantly those with eye tumors, brain tumors, or tumors in the area of the head and neck and pelvis. This broad clinical experience has shown very clearly that, compared to photon therapy, it is the spatial precision in applying the radiation, which is of decisive importance. This provided the motivation for PSI specialists to develop a new proton therapy facility for high-precision irradiation of deep-seated tumors. The PSI gantry has been in operation since 1996 and by end of 2012, more than 900 patients had been treated with protons.

Melanomas of the eye
In 1984 the first treatments with protons of eye tumors in Western Europe were carried out at PSI. By end of 2012 we had treated allmost 6000 malignant eye tumors with the OPTIS proton therapy facility. The therapy success rate includes more than 98% of the primary tumors being cured and in 90% of the cases the eye could be saved.

Spot-Scanning for deep-seated tumors
The success rate of the eye treatments and the good experience with proton therapy for other indications at the Harvard Cyclotron Laboratory in Boston provided the motivation for the PSI specialists to develop a new proton therapy technique for high precision radiation of deep-seated tumors. For this installation a pencil beam of protons is computer controlled in such a way that high dose spots of protons can be positioned very precisely, for an exactly specified period of time and at any desired location within the tumor. By superimposing many different spots - about 10,000 within a volume of one liter - the radiation dose can be distributed uniformly over the entire tumor. This is the principle of the Spot-Scanning Technique implemented into the PSI-Gantry.

About 80 patients were suffering from meningiomas. These tumors arise from the coverings of the brain (the meninges) which are located between the bones of the skull and the surface of the brain. They grow slowly, displacing adjacent structures, and may infiltrate the surrounding cranial bone. Depending on location and size, they may cause severe headaches, epileptic attacks, disorders of brain function, episodes of loss of consciousness, paralyses and other neurological defects. If surgical removal is impossible, the precise spatial adjustment of the radiation dose involved in proton therapy offers particular benefits.

Brain tumors
More than 140 treatments have been carried out for patients with brain tumors (for example: gliomas, ependymome, medulloblastome). Most such tumors arise from glial cells, the supporting cells of the brain tissue, and the more closely they resemble the cells from which they originate, the more likely they are to respond well to treatment. In these cases we refer to tumors as grade 1 and 2. When the tumor cells have developed differently to the original cells, so called (entdifferenziert) then proton therapy cannot promise more than photon radiation as the whole brain must be evenly treated. These grade 3 and 4 tumors and glioblastomas are not part of the treatment program at PSI. These tumors are usually treated in clinics with a combination of chemo- and radiation therapy.

Chondrosarcomas and Chordomas
More than 500 patients were referred for proton therapy because of chondrosarcomas or chordomas involving the base of the skull or the spinal axis. Such tumors are of connective tissue origin, grow slowly and very seldom metastasis, but destroy the most susceptible adjacent structures, often those which are essential for life. The cranial nerves are located at the base of the skull, the optic nerves are close by, as also is the optic chiasm. Permanent damage to these structures is likely to cause blindness. The brainstem, as a part of the central nervous -system, cannot tolerate persistent pressure from a tumor, far less actual invasion, but it also has limited tolerance towards irradiation.

Because the proton beams stop at a calculable depth, depositing most of their radiation load within this stopping region (the Bragg peak), chordomas and chondrosarcomas of the skull base have for many years been treated by irradiation. This has become the subject of a well organized clinical trial conducted mainly with the Harvard cyclotron at Massachusetts General Hospital in Boston. Convincing success has been achieved: for chondrosarcomas local tumor control has been raised from about 40% to over 80%, while for chordomas it is now about 65%. These tumors, like melanomas of the eye, have therefore become an indisputable indication for proton therapy. We have achieved successful tumor control for our patients, together with general well-being and a highly satisfactory quality of life.

Sarcomas – malignant tumors arising from the connective and supporting tissues – also occur in other parts of the human body, for example, in the coccyx, in the lumbar vertebral column, on or within bones and joints and also in muscle tissue. Up until middle of 2012 we treated more than 150 patients, with sarcomas not in the spinal or scull base area. Some of these treatments were in partial combination with surgery and or chemotherapy and appear to be successful so far.

Prostate Cancer
Up until the end of 2003, we treated 13 cases of prostate cancers with protons. These treatments were likewise successful, and the patients are doing well. From 2004 on there was not the capacity to treat any prostate cancer patients and the health insurance system in Switzerland is not covering the costs for prostate cancer treatment with protons.

ORL tumors
Tumors in the ear, nose and throat region (ORL tumors) often grow in close proximity to the sensitive structures of the brain, the base of the skull or the spinal column. Up to 2012, we had treated more than 50 ORL tumors (including two skin tumors), in partial combination with surgery, chemotherapy and, in some cases, also with conventional radiation.

Children and youth
Until end of 2012 we treated more than 250 children and youth between the ages of one and twenty-years old. About 150 of these, between the age of 1 and 5, had to be treated under anesthesia, in order that they remained absolutely still during the treatment. The tumors were located in the scull or the base of the scull and between 14.0 and 74.0 CGE was applied. In some cases this was also in combination with conventional photon radiation treatment.

Age distribution of patients
More than 60 % of patients were under 40 years of age, while more than 50% are today children and young people under 20. Such patients derive particular benefit from proton therapy, because the precise delivery of the highest radiation dose within the tumor minimizes damage to the vulnerable and still growing body of the child or young person. It also means that subsequent, secondary tumors are less likely to arise than after photon therapy.

Intensity-modulated proton therapy (IMPT)
PSI operates world's only facility able to treat patients with intensity-modulated radiation therapy with protons (IMPT). First patient treated with IMPT was a young male patient, suffering from a chondrosarcoma of the upper thoracic spine in 1999. Once again, our objective was to control the tumor, while giving the best possible protection to the immediately adjacent spinal cord, so as to preserve the working capacity and quality of life of this 36 year-old man. Seven years after the conclusion of the therapy, he is free of symptoms and working full time. We have further developed this technique, and in the past years more than 50 % of the patients were treated fully or partialy with IMPT.

Prospects for curing tumors with proton therapy
In over 80% of the cases treated we have been able to stop the growth and kill the tumor, curing the patient. The remainder of the patients had such an advanced tumor growth or it was metastasized so that despite the tumor being controlled the patient was not cured. However in many cases an alleviation of suffering was achieved, and treatment also slowed advancement of the disease. This was achieved with nearly no side effects. Unfortunately, in some cases the tumors grew again.

Clinical experience – future developments
The clinical results achieved so far seem to reliably indicate that the developments in proton radiation techniques can offer patients with certain cancer indications considerable benefits in therapy and healing. Under the project PROSCAN the facility is being continously expanded and by 2014 we will be able to treat about 250 to 300 patients with deep seated tumors on a year-round basis. Due to the technical capabilities of the new Gantry 2, moving tumors will also be treated with the high precision scanning treatment technique at PSI. An additional treatment room (Gantry 3), which will have similar features as Gantry 2, will be installed beginning of 2014 and used for clinical research from 2016 on.