PATIENT-HOTLINE

Patients and relatives can contact short at this point of contact for questions, suggestions and criticism.

+49 (0) 89 660 680

We are there for you at the following times

Monday to Friday from 8.00 am to 6.00 pm

Contact

RINECKER PROTON THERAPY CENTER
Franz-von-Rinecker Straße (main entrance)

Schäftlarnstraße 133 (postal address)

81371 München

Do you have any questions?
+49 (0) 89 660680

About us

The RINECKER PROTON THERAPY CENTER

The RPTC, located in Munich, is the first fully certified European proton radiation center which provides a complete hospital setting for the treatment of cancer tumors.

Our innovative therapeutic procedure involves the use of high-energy proton beams for the treatment of cancer. A key characteristic of these proton beams is that protons facilitate the three-dimensional targeting of tumours; this capability is not available with the x-rays used in conventional radiation therapy. Therefore, highly effective dosages can be delivered to the tumour while the side effects of radiation are reduced by minimizing any trauma to the surrounding healthy tissue.

Questions? +49 (0) 89 660 680

RINECKER PROTON THERAPY CENTER THIRD ANNUAL REPORT ESTABLISHING PROTON CANCER THERAPY IN EUROPE
2012-05-06 11:34

RINECKER PROTON THERAPY CENTER THIRD ANNUAL REPORT ESTABLISHING PROTON CANCER THERAPY IN EUROPE

RINECKER PROTON THERAPY CENTER THIRD ANNUAL REPORT ESTABLISHING PROTON CANCER THERAPY IN EUROPE

THE EXPERIENCES FROM THE IRRADIATION OF THE FIRST 1,000

PATIENTS

 

 

MARCH 2012

 

 

CONTENT

  • WE NEED AN INNOVATIVE CANCER THERAPY
  • THE WORLDWIDE WHO-IS-WHO OF RADIOTHERAPY WITH PROTONS
  • As a refresher: THE ESSENTIAL BENEFITS OF PROTON THERAPY AND THE ESSENTIAL QUESTIONS
  • ACTIVITY REPORT TO MARCH 2012 – THE FIRST THREE YEARS, THE FIRST THOUSAND PATIENTS 
  • CLINICAL RESULTS:

    Proton Therapy of Liver Metastases

    Proton Therapy of Intracranial Meningiomas

    Locally Advanced Pancreatic Cancer

    Early Results with „Normal“ Prostate Cancer

    High-Risk Prostate Cancer

    Chordoma

  • WHAT WE ARE WORKING ON NOW
  • COST COVERAGE BY PUBLIC AND PRIVATE HEALTH INSURERS 
  • OUR TEAM
  • LITERATURE 

 

 

 

 

WE NEED AN INNOVATIVE CANCER THERAPY 

 

In 1981, the Robert Koch Institute in Berlin estimated 269,000 new cases of cancer for the area of today‘s Federal Republic of Germany. The estimate for 2012 is 482,000 new cancer cases, an average increase of approximately 7,000 new cancer cases in Germany year after year, at a roughly constant population size. If even the prophylactic measures in the past 30 years did not achieve a reduction of the probability of disease, did improvements in therapies at least reduce the number of resulting deaths? The answer is no: Every year, there were approximately 3,000 more cancer deaths! Does each of us – after this past – have an ever greater chance of dying from cancer in the future? The answer is, unfortunately: yes. Therapeutic advances have not kept pace with the increase in cancer incidence.

 

If the 1,800 childhood cancers each year, which originate from the rapid growth phases in the womb and from early childhood, are not taken into account, the increasing incidence of cancer can be explained by the „stochastic“, which means random, occurrence of cancer degeneration after an initial resting phase, for each year of one‘s life across the individual’s entire old age. In other words, the increase in life expectancy by 10.3% worldwide – about 7 years in Germany – during these last 30 years is the cause for and goes hand in hand with the rise in cancer cases.

 

In previous annual reports (www.RPTC.de) we have tried to describe the superiority of proton scanning, over all including the latest X-ray irradiation methods and the „heavy-ion“ particle therapy in theory, based on international clinical results. Our own experience with the first 1,000 patients who have completed treatment at the RINECKER PROTON THERAPY CENTER, the first such therapy facility in Europe, have confirmed – or surpassed – these findings.

 

Surgery is used less frequently (prostate cancer, brain tumors). Chemo- and immunotherapies alone help to prolong the life of patients with solid tumors (four to six months), but they are not curative. Particle therapy with "heavy ions" was abandoned in the context of new health care services (stop in Marburg and Kiel).

 

In all of the more than 1,000 patients treated by proton scanning at our facility, the healthy surrounding of the tumor was exposed to significantly less scattered radiation. And the effective tumor dose was at least equal, usually higher. For one quarter of our patients, irradiation by X-rays had technically not been feasible, or they had already received unsuccessful X-ray irradiation.

 

Proton therapy is finally the innovative cancer therapy. The transition to proton therapy has taken place in the United States with 10 systems in clinical use, 9 under construction and 5 in process of planning. In Europe, the RINECKER PROTON THERAPY CENTER is the leader in this field.

 

Hans Rinecker, PD Dr. med. Dr. med. habil. 



 

THE WORLDWIDE WHO-IS-WHO OF RADIOTHERAPY
WITH PROTONS 

 

James M. Slater Proton Treatment and Research Center Loma Linda University,

Loma Linda, Kalifornien, USA

 

3 gantries, 1 fixed beam, proton scattering, 250 MeV synchrotron

 

The prototype of today‘s proton therapy facilities for the whole body: Clinical operation commenced in stages beginning in 1992. First, the system operated with doses that are comparable to conventional x-ray therapy, which, as expected, did not lead to an improvement in clinical results, but because of the lack of side effects caused a great popularity of the institute. After one had dared to increase the dose, the facility delivered outstanding results, particularly for prostate carcinoma (Reference 1). The scattering method used in Loma Linda was an interim solution that delivers far better results than x-ray therapy, but the local dose distribution in comparison to proton scanning is not optimized. (Figure 1).

 

 

Francis H. Burr Proton Center, Harvard University, at the Massachusetts General Hospital, Boston, Massachusetts, USA

 

2 gantries, 1 fixed beam, proton scattering, 230 MeV cyclotron

 

The first proton therapy system produced by the medical device industry (Figure 2). The Massachusetts General Hospital, number seven in the national ranking of the best U.S. hospitals in cancer treatments (2011 U.S. News & World Report), together with the Harvard Medical School had already gained extensive experience with proton therapy in the 1960s at the old Harvard cyclotron, in particular on the head. In the 1990s, a follow-up system with 2 gantries using the scattering method, the forerunner method of the advanced scanning method used at the RPTC, was therefore built based on the model in Loma Linda. This system commenced patient treatment in stages starting in 2001. The Center in Boston can look back on the longest experience with proton therapy, and still acts, in conjunction with the Harvard Medical School, as an international training center for radiation oncologists and medical physicists. A number of key scientific studies comes from this facility, such as the development of the double-scattering method, various protocols, especially in the skull, and major publications, for example, by Herman Suit (Reference 2).

 

 

  1. D. Anderson Cancer Center´s Protoncenter

University of Texas, Houston, Texas, USA

 

3 gantries, 1 fixed beam, partitial proton scanning, 250 MeV synchrotron

 

The MD Anderson Cancer Center in Houston is one of the world's leading centers for cancer therapy: In 2011, the hospital ranked first for the fifth consecutive year in the annual rankings (U.S. News & World Report). Consequently, the Center has already started at the beginning of this millennium with the planning and construction of a proton therapy facility. Clinical operation commenced in 2006. Since then, the four treatment rooms have been expanded in stages. The MD Anderson Institute was, besides the RPTC in Munich, the first to utilize modern proton scanning technology in a large clinical facility. In contrast to the RPTC, however, the scanning system in Houston is a multi-functional version with sub-optimal scanning results. Moreover, not all gantry treatment rooms are equipped with scanning. MD Anderson was the first of the world's undisputed leading cancer treatment centers to rely on the proton therapy method (Figure 3).   

 

 

Roberts Proton Therapy Center

University of Pennsylvania, Philadelphia, Pennsylvania, USA

 

4 gantries, 1 fixed beam, mainly proton scattering, Multileaf Collimator,230 MeV cyclotron

 

As one of the most prestigious and oldest universities on the US East Coast, the University of Pennsylvania has set up the largest proton therapy center in the States so far. It has – as the RPTC – five treatment rooms, four of which are equipped with gantries. Treatment of patients started in 2010. Originally, the center was designed as a pure proton scattering system. Attempts were made early on through the integration of so-called multileaf collimators to eliminate some of the weaknesses of the scattering process at least partially. Recently, however, one of the gantries at this center was equipped with a combined scanning system (Figure 4).  

 

 

Proton beam therapy program at Mayo Clinic

Zentrum 1: Mayo Clinic, Rochester, Minnesota, USA

Zentrum 2: Mayo Clinic Phoenix, Arizona, USA

 

4 gantries each, complete proton scanning, 250 MeV synchrotron

 

The Mayo Clinic, which operates the world's largest Cancer Center at three locations with more than 20,000 patient admissions per year, has started a proton therapy program. Two treatment centers are being built within a short time interval. The first is built on the Mayo Clinic campus in Rochester, Minnesota. The laying of the foundation stone took place in September 2011, the first patients are to be treated in 2015. The second treatment center will be built on the Mayo Clinic campus in Phoenix, Arizona. The laying of the foundation stone took place in December 2011, the first patients are to be treated in early 2016. Both centers with their treatment rooms will then be taken into clinical operation step by step and each will reach full capacity in 2017. The Mayo Clinic is the first institution in the United States that exclusively relied on the proton scanning method and will equip each of the four treatment rooms with gantries and a dedicated scanning system (Figure 5).

 

 

The Proton Institute of New York

New York City, New York, USA

 

4 gantries, 1 fixed beam, partial proton scanning, 230 MeV cyclotron

 

The world‘s most prestigious cancer centers in New York City have joined a consortium in 2010 to build the New York Proton Institute. This includes in particular the Memorial Sloan-Kettering Cancer Center, Beth Israel Medical Center, New York University NYU Langone Medical Center, Montefiore Medical Center and Mount Sinai Hospital. The center is currently under construction in Manhattan. Patient treatment is planned for 2014. Not least because of these famous hospitals, in the United States the die has been cast in favor of proton radiation oncology (Figure 6) and (Figure 7).  

 

 

RINECKER PROTON THERAPY CENTER

RPTC, München, Deutschland

 

4 gantries, 1 fixed beam, proton scanning on all gantries, 250 MeV cyclotron

(superconducting)

 

Commencement of clinical partial operation in March 2009, full expansion in 2012. With regard to performance, the facility is specified for the first time up to the physically possible limits of proton irradiation: it is, therefore, the world‘s most advanced facility. In the meantime, these specifications have all been technically implemented at the RPTC. The system therefore represents the prototype of „mature“ proton technology; the specifications regarding penetration depth, intensity of the beam, delicacy of the beam, and the precision of targeting cannot be exceeded any more in the foreseeable future because of these physical limits. The performance data are therefore the world‘s best, and not only for the time being (Figure 8).

  

 

Other facilities

 

Worldwide, there are currently 25 proton therapy facilities in operation, which reach a proton energy, and thus a penetration depth, that allows the treatment of deep seated tumors throughout the body.

 

Table 1: Proton therapy facilities for treatment of deep seated tumors (March 2012)

 

In addition, a number of proton therapy facilities is still in operation, working with smaller particle accelerators and which are, therefore, usually used on the eye only:

  

Table 2: Proton therapy facilities in operation for near-surface tumors

 

Worldwide, a large number of proton therapy facilities are under construction – proton

therapy will take over patient care.

 

Tabelle 3: List of proton therapy facilities currently under construction worldwide (March 2012)

 

As a refresher: THE ESSENTIAL BENEFITS OF PROTON THERAPY – AND THE ESSENTIAL QUESTIONS 

 

Cancer therapy using ionizing radiation has been one of the pillars in medicine for over a 100 years. The basic principle of radiotherapy is that any ionization can cause damage to a cell, be it a tumor cell or a healthy cell. The probability of cell damage and, in the case of a tumor cell, the desired cell death, only depends on how much radiation dose can be brought into the tissue through irradiation. With modern radiotherapy equipment – no matter what version or type of radiation – one can theoretically always directed a sufficiently high, sterilizing dose into the tumor.

 

At the same time, however, the crucial problem of radiation therapy is revealed here: The tumors to be irradiated are typically located within the body and are surrounded by healthy tissue. If healthy tissue is exposed to radiation doses, it may also get damaged. With certain organs, this may happen even at a much smaller dose than would be needed for the sterilization of the tumor; particularly for tumor localizations close to vital organs or the brain this may lead to extreme collateral damage and make therapy impossible.

 

The main role of radiotherapy is, therefore „to get as much radiation dose into the tumor, while at the same time sparing healthy tissue optimally.“ If radio-oncologists are unable to meet this task in a particular treatment situation, they will usually limit the dose to protect the healthy tissue in the tumor environment. But this leads inevitably to a low control or cure rate!

 

Today, most patient treatments are carried out using high energy X-rays. No matter whether this radiation is generated by X-ray tubes, radioactive sources or electron linear accelerators, there is always the distinct disadvantage of the physical interaction of electromagnetic waves with matter: The radiation dose deposited in an irradiated body decreases exponentially with the body depth (see Figure 9, orange curve). This means that in the beam direction in front of the tumor one will always administer a higher dose to healthy tissue than to the tumor, and behind the tumor there will also be a significant radiation dose effect.

 

The critical breakthrough for the patient and his chances of recovery as well as the side effect rates occurred with the introduction of a new type of ionizing radiation in radiation therapy: High-energy accelerated protons. The main difference lies in the different physical mechanisms of interaction with the irradiated matter: Protons as so-called heavy charged particles release their kinetic energy only gradually while passing through matter. Most of the energy is deposited only at the end of its path, in the so-called Bragg peak (see Figure 9, green curve). This adjustable range of proton beams in the tissue, which is based on purely physical effects, enables, finally, the three-dimensional targetability needed for a highly efficient radiotherapy! Proton beams allow to reduce the damaging dose – its depth localization depending on the speed of the protons, and hence is controllable in healthy tissue – in front of the tumor by a factor of three to five in comparison to X-rays. At the same time, due to the defined penetration depth and the range of the proton beams, no dose is deposited any more behind the tumor.

 

Proton therapy finally provides the radiation therapist with the tool that enables him to bring the desired high radiation dose into the tumor while sufficiently sparing surrounding healthy tissue and to avoid side effects with this, now three-dimensional, targetability.

 

At the RPTC proton therapy facility the penetration depth can be defined with a precision in the submillimeter range. And with a penetration range up to 38 cm in water, which corresponds to a kinetic proton energy of 250 MeV (mega electron volts) (see also the measured depth dose curves, Bragg peaks at the RPTC, Figure 10).

 

Jörg Hauffe

 

    

How does proton therapy work technically?

 

The best way to understand how proton therapy works technically is to take a look at the physics and technology inside the particle accelerator and beam line.

  • By means of electrolysis, hydrogen is produced from water in small quantities.
  • The proton begins its journey in the so-called ion source: In fractions of seconds, the hydrogen atoms are split into negatively charged electrons and positively charged protons in an electrical arc.
  • In the particle accelerator, the cyclotron, the protons can be extracted from this ion source area due to their electrical charge by means of electrical fields and consequently in 650 spiral paths accelerated to 250 million electron volts. They exit the particle accelerator after 3 microseconds at a speed of 180,000 km per second in a vacuum beam tube.
  • To adjust the energy of the protons as needed for the patient’s individual tumor depth, the proton beam then flies through the energy selection system. Arranged in a vacuum, a series of graphite wedges and copper apertures can be adjusted by electric motors in seconds so that the protons will find an appropriate braking distance, and thus have exactly the necessary speed and penetration depth. Using sophisticated electromagnets, the beam is then again compressed to very small dimensions.
  • After the energy selection, the protons move in a vacuum tube through the beam transport system. It consists of a plurality of electromagnets, which focus the proton beam, correct for minimal positional deviations, and deflect the proton beam to the five treatment rooms by means of „magnetic switches“.
  • In the treatment rooms the protons are also seamlessly passed on in a separate beam transport system to the gantry and then to the patient.
  • Each gantry in the four major treatment rooms can be rotated by 360 degrees. Together with the patient table, which has six degrees of motion, the proton beam can be targeted at the tumor from any direction.
  • The scanning magnets, i.e. the last electromagnet unit, sit in the so-called
  • nozzle (the beam exit in front of the patient). These ultra-fast coils deflect the
  • proton beam in the millisecond range in the x- and y-directions. This is done
  • according to the scan pattern derived from the treatment plan in up to 25,000
  • individual overlapping spots that are positioned in individual layers covering the
  • tumor using the energy selection (see Figure 10 above).
  • A number of detectors and monitoring systems are implemented in this treatment system to ensure that each patient will receive the prescribed proton dose with the appropriate spatial dose distribution. More than 6,000 parameters are continuously monitored and checked for accuracy, many of them every few milliseconds, some even every few microseconds.
  • The proton travels 2.1 km from the ion source to the patient in the most remote gantry (about 2 km of which inside the cyclotron) and needs 3.5 microseconds for this journey.
  • We need much less hydrogen gas than would fit into a bubble of champagne to cure a patient.

 

What is proton radiation? 

 

Protons are elementary particles of matter. All matter is made of atoms. Atoms in turn are made up of the atomic nucleus and atomic shell. Atomic nuclei consist of protons and neutrons. The simplest way to obtain individual protons is to break up the smallest atom, namely hydrogen, in its two components, an electron and a proton. Protons themselves are stable and therefore do not „radiate“. The term proton beam refers to protons that are accelerated to high velocity in particle accelerators. They emit their kinetic energy when they enter into and interact with matter in the form of ionization. Accelerated protons are therefore called ionizing radiation.

 

How long does the proton radiation remain in the body?

 

In proton therapy, proton speeds are calculated by medical physicists in the so-called treatment plan so that the protons „get stuck“ in the tumor. Since the accelerated rotons emit kinetic energy completely in the tissue and at the end of their life they donot have any kinetic energy left behind the so-called Bragg peak, they cannot trigger any further ionizations. Then there is no more proton radiation left. The protons themselves are absorbed by the matter. One should keep in mind that the amount of protons that are introduced into the body during a treatment session is tiny – i.e. only about 2.4 pg (this is: 2.4 * 10-12 grams). After termination of the daily treatment session, patients may leave the treatment room, and they do not emit any radiation and do not endanger other persons.

 

What side effects may occur and are there any risks?

 

In general, side effects, if they occur, can be reduced compared to X-ray therapy, for example, on the neck to 1/3 to 1/5. This is the consequence of the concentration of the proton ionization in the target area due to physical reasons, compared to X-rays. This is crucial for patients’ quality of life and well-being. For example, some patients suffer from persistent dry mouth following radiotherapy due to the nearly unavoidable exposure of the salivary glands to radiation. This causes discomfort when talking, and also during the daily food intake. Proton treatment can prevent these side effects. Whether and what side effects may occur even with protons depends very much on the particular indication and, of course, on the body region being irradiated. The physician will explain this to the patient in more detail during the consultation.

 

Which tumors can be treated by means of protons?

 

In principle, any tumor that can be irradiated using conventional X-ray radiation therapy can also be irradiated with protons. In addition, proton therapy is also suitable for tumors that previously were not accessible to irradiation because they were too close to vital organs. Details can be found in the spectrum of treatment and in the list of tumors already treated at the RPTC. However, only the radiation therapist with formal and technical qualifications in proton therapy can decide whether proton irradiation is indicated in a particular case; he or she makes this decision using your medical records and images that are already available.

 

What are the chances of success?

 

Basically, a definitive cure is possible through proton therapy. This will always be the goal, provided there are not already several metastases present. However, this depends on the particular disease and the particular stage.

 

Does the patient feel the radiation?

 

Radiation cannot be felt by patients and is completely painless; in addition, each session generally lasts only 60 to 120 seconds. Therefore, adults are not anesthetized for radiation treatments. However, children, who tend to be less calm, are sometimes given light, short-term, fully monitored anesthesia so they do not move allowing the beam to be precisely guided to the tumor. Anesthesia is also beneficial if organs that move with respiration, such as the lungs or liver, are being irradiated, since these organs move a few centimeters during normal spontaneous respiration. This would prevent us from irradiating the tumor in a single pass and reduce the precision of treatment. For this reason, we administer anesthesia to the patient and after controlled ventilation with 100% oxygen, „apnea“ is induced for the brief radiation period to ensure the tumor is „stationary“ and can be precisely targeted. For small children, an additional form of anesthesia is used: a light twilight sleep during which the child breathes spontaneously and only „sleeps“ during the actual procedure. Continuous monitoring and control by anesthesiologists ensures the safety of our patients at all times.

 

How long does proton therapy take?

 

The length of treatment, indicated by the number of daily radiation sessions, is different for each patient and depends on the particular tumor and the tumor localization. One treatment session is scheduled every day. The typical number of sessions (fraction number) is shown in Figure 11 below. Currently, the RPTC holds 21 sessions for prostate cancer treatments (conventional radiology usually 41).

 

How is my condition after treatment or after therapy?

 

In general, the tolerability of proton therapy is excellent. Whether and what side effects may occur even with protons depends on the particular indication and the body region affected. The physician will explain this to the patient in more detail during the consultation and provide information on measures should any side effects occur. For example, if skin and mucous membrane irritations occur, we use a medical laser to minimize radiotherapy-induced problems. The current state at the end of therapy and tips on how to behave and what to do during the following period are the subject of the planned final discussion with the doctor.

 

Is proton therapy suitable for children? 

 

Yes. The ability to guide the radiation dose with high-precision and three-dimensionally controlled to the target area – the tumor – makes proton therapy an ideal tool for treating childhood cancer. Proton therapy in particular provides accurate treatment of tumors near or within sensitive organs while minimizing radiation exposure to healthy tissue. This is of vital importance in children whose bodies are still growing and developing. Proton therapy helps to reduce side effects during treatment, often allowing children to better tolerate proton therapy. In the U.S., the irradiation of children (under 16 years of age) by X-rays instead of by protons is already widely regarded as malpractice.

 

How can a patient get treatment at the RPTC?

 

The first contact point is the patient‘s hotline: +49 (0) 89 660 680. Patients can obtain basic information and request brochures and registration forms. We have also set up a special hotline for doctors. A radiation oncologist of the RPTC is available for technical information under telephone number +49 (0) 89 452 286 2268 from Monday to Friday from 08:00 a.m. to 4:00 p.m. 

 

Can mobile tumors (lung cancer) also be treated?

 

Organ movements are a fundamental problem in radiation therapy, not only in

proton therapy, because they always require a higher planning volume – that is, a larger

safety margin around the tumor. Of course, proton therapy preserves the favorable

ratio of helpful to harmful radiation to protect healthy tissue regardless of planning

volume.

 

Several methods are used successfully in X-ray and proton radiotherapy to ensure with the greatest possible certainty that mobile organs are always irradiated in the same position, and thus to minimize the safety margins: The prostate, for example, can be immobilized by using a rectal balloon which brings the prostate in a specific predefined position. Alternatively, the prostate can be marked with gold beads that can be adjusted into the desired position during X-ray position monitoring performed prior to each irradiation session. There are two options for immobilizing organs that move with respiration, such as lungs or liver. One is the so-called respiratory gating. Here, the respiratory excursion (degree of pulmonary emphysema) is measured and the beam is released only during the correct respiratory position. A better, more accurate method is irradiation during apnea, which is used at the RPTC; it means the anesthetized patient is irradiated during a brief respiratory stop in a precisely defined position. The lung is flooded with oxygen. For more information please see the Activity Report below: „Precision irradiation using the proton scanning method in respiratory arrest“.

 

Is proton therapy ever combined with other forms of cancer treatment (surgery, chemotherapy, etc.)? 

 

Yes. Many times lung cancer, lymphoma, or childhood cancer are simultaneously treated with proton therapy and other types of therapy, such as chemotherapy. Depending on the case and type of cancer, proton therapy may be used in combination chemotherapy and/or surgery. The doctors at the RPTC will check in each individual case whether such a combination therapy is an adequate option. The radiation therapists at the RPTC can present these cases to other colleagues, namely surgeons, hematologic oncologists, urologists or pediatricians at the RPTC Tumor Board. As part of an integrated treatment network involving the CHIRURGISCHE KLINIK DR. RINECKER (Surgical Clinic Dr. Rinecker) and hematologic oncologists and internists at the Internistische Klinik Dr. Müller (Dr. Müller Internal Clinic) and the children‘s department of the Klinikum München Schwabing (Munich Schwabing Hospital), all combination therapies can be performed immediately.

 

How exactly will a patient be positioned for therapy each day?

 

Proton therapy at RPTC is a high-precision radiotherapy requiring the daily reproducible precision positioning of the patient. For this purpose, each patient being treated at the RPTC receives an individually adapted whole-body fixation molding before treatment. This consists of polystyrene beads, which are sealed in a plastic bag. Through evacuation, this mat can be adapted precisely to the patient‘s shape. It is stored at the RPTC throughout the treatment period and is preserved in its ideal form by a special pump and control procedure developed at the RPTC. The patient is positioned in this fixation molding for its daily irradiation outside the treatment room. During the daily irradiation, in most cases, a foil is placed over the patient and glued to the fixation molding. Vacuum pumps ensure an additional „press fitting“ of the patient in the fixation molding and thus an even better fixation and, therefore, precision. In addition, a bite block is made for treatments in the head area. This bite block is manufactured – similar to those made by the dentist – directly at the RPTC. A small pump generates in addition a negative pressure which draws this bite block to the upper palate. These mechanical positioning aids ensure a highly accurate fixation of the patient during proton irradiation. Minor variations in patient position that are still possible can be detected by the patented X-ray position verification system immediately before each irradiation of each patient. A complex computer process then determines in seconds if a position correction with a precision in the submillimeter range is required for the patient table in the treatment room. This patient table can then be moved in six axes to achieve the best possible positioning of the patient.  

 

Is proton therapy technique safe?

 

Our proton scanning has introduced an entirely new safety standard in radiation therapy.

 

Today, a so-called computer-aided treatment plan has to be created for all irradiations with all types of radiation. Cross-sectional images of computerized tomographies prepared specifically for this purpose (sometimes combined with magnetic resonance images) are used. A radiation oncologist with expertise in proton therapy defines with a cursor the target area including the tumor, its nearby dissemination, for example, to the lymph nodes, and a certain safety margin. The specialist also indicates those areas and surrounding organs that must be preserved during the irradiation. These electronically recorded „recipes“ are then signed by two radiation oncologist with expertise in proton therapy according to the four-eye principle – again using biometric-electronic iris recognition. A certified medical physicist, also with expertise in proton therapy, then translates this radiation recipe into technical plans, again electronically, for the irradiation machine. This usually requires several computer-aided iterations (cycles) to determine the best irradiation configuration, i.e. the best coverage of the target area, while sparing the organs at risk as much as possible. This six-eyes principle physician/physicist is required by law and in our operating license!

 

The positioning of the patient, which will not be discussed here, rules out incorrect positioning and body movements during the short period of irradiation. The exact positioning of the patient in the treatment beam is done at the RPTC using a patented X-ray-based system which, we believe, is the best available today. Together with the accuracy of the proton beam, alignment errors are in the range of one millimeter. Irradiation, therefore, is safely planned and precise.

 

As stated above, irradiation takes place in the proton scanning system in individual, a few millimeters wide spots with overlapping doses. Completely new is that the dosage of each single one of these up to 25,000 spots – with a large tumor – are measured individually and documented.

 

With now over 95 million single spots, no dose deviations were detected in these single (!) spots that were above a tolerance of 1 to a maximum of 3% – in X-ray procedures one expects 3% on average. In only one of these irradiation sessions, the schedule for the individual sessions was processed too quickly, due to an operating error by a medical physicist. In the meantime, however, this kind of operating error will be prevented by additionally implemented control software. The patient received a higher dose in the tumor than planned. This dose, however, was still below that used by other methods for the prostate (Brachytherapy). And above all: The excellent focusing of the proton beam within the target area only has exposed the patient‘s healthy tissue to a lower radiation dose than would have been the case with „normal“ X-ray irradiation.

 

How often does the proton therapy facility have to be serviced?

 

The proton therapy system at the RPTC is a high-tech medical product. The system has been CE certified in accordance with European directives and inspected and approved in a complex licensing process by the competent authority, the Bayerisches Landesamt für Umwelt (Bavarian Environment Agency) (LfU). In addition, in accordance with the regulations imposed by German law, the system is regularly reviewed by sworn-in technical experts on behalf of the LfU and the RPTC. To ensure the highest possible availability of the system for patient treatments, the RPTC has therefore signed a comprehensive maintenance contract with the manufacturer. Staff of the company Varian is available 24 hours, 7 days a week at the RPTC. During this time, they carry out both regular maintenance work, especially through the night hours and on Sundays, and repair work at a very fast response time. At the RPTC, we have thus achieved an average availability of about 96%. Several times a year, more time-consuming maintenance work is carried out by the manufacturer, including preventive maintenance; this maintenance work is performed on a Saturday and a Sunday. In addition to maintenance work, the RPTC staff, i.e. the medical physicists, carries out extensive daily quality assurance measurements and analyses of the therapy system before the start of patient irradiations. This will ensure and document that the proton therapy system at the RPTC meets our highest standards in terms of precision, reliability and safety at any time.

 

Are interruptions in therapy likely?

 

The technical availability of the proton therapy system at the RPTC for patient treatments is very high – still, however, it may happen that the quality assurance procedure carried out every morning by the medical physicists indicates that system performance is not optimal. Moreover, the high-tech equipment used at the RPTC is not immune to problems, so that occasionally a computer system, a cable or an electric motor may fail and have to be replaced. In these situations the proton therapy system is not available for patient treatment in one or several treatment rooms until the defects have been corrected. In the first three years of operation, the technical design of the system by the manufacturer and the RPTC has been confirmed, i.e. we never once had a standstill for more than one day at a time. The radiation therapists at the RPTC have considered such situations in their therapy concepts, so that this has no effect on the clinical success of the therapy.

 

Are there other doctors than radiation therapists at the RPTC?

 

Yes. The permanent RPTC team includes, besides radiation therapists, a specialist in radiodiagnostics, who performs all staging examinations on our MRI, CT and PET/CT devices. In addition, we are supported by a specialist in nuclear medicine in the implementation and evaluation of the PET diagnostics. Since a range of treatments at the RPTC is carried out in anesthesia, we have our own specialist in anesthesiology. He is the head of this department and performs and monitors all anesthesias. Furthermore, we have a consulting physician for urology at the RPTC, who treats urology patients, particularly prostate cancer patients, at the RPTC. He conducts examinations using ultrasound technology and prepares the treatment of patients at the RPTC. A consulting physician for hematological oncology takes care of all of our patients who are in need of chemotherapy before, during or after proton therapy. He looks after the patients, both directly at the RPTC and in the Internistische Klinik Dr. Müller (Dr. Müller Internal Clinic), located in a distance of only 200 meters from the RPTC. Since the RPTC is both in form and content closely linked with the CHIRURGISCHE KLINIK DR. RINECKER (DR. RINECKER SURGICAL CLINIC (CKR)), and the nursing beds for in-patient stay in hospital for proton therapy are located in the CKR, all specialists of the CKR are also available. These are specialists in heart surgery, general, vascular, accident and visceral surgery, emergency medicine specialists, plastic and aesthetic surgery, neurosurgery, specialists in anesthesiology and intensive care medicine and radiology. In the treatment of children we cooperate closely with the Klinikum München Schwabing (Schwabing Municipal Hospital), whose pediatric department is also part of the Clinic of the Technical University of Munich. Children who need in-patient care are treated there.

 

Is proton therapy experimental?

 

No, proton therapy is neither experimental nor is it the subject of basic research. It has been used in the United States for more than 50 years and in a hospital setting since 1990. To date more than 85,000 patients have been treated worldwide. Proton therapy is an established form of cancer treatment that is widely accepted by physicians, government agencies and many insurers. In the course of the official approval procedure, the Bundesamt für Strahlenschutz (Federal Office for Radiation Protection) has come to the conclusion that the proton therapy practiced at the RPTC is no longer to be considered research, but as an established method for routine „Application in Human Medicine“. Accordingly, the operating license for the RPTC was issued by the Bayerisches Landesamt für Umwelt (Bavarian State Office for the Environment).

 

What if the insurance does not pay but I still want proton therapy?

 

The RPTC patient management is experienced in working with domestic and international patients who are interested in making arrangements to pay for their care directly.

 

How long is the wait for an initial consultation or the start of treatment?

 

You can reach the RPTC at any time by calling +49 (0) 89 660 680 or by e-mail (patient@rptc.de). The patient‘s medical practitioner may also contact the RPTC doctors at the Medical Hotline +49 (0) 89 452 286 2268 from Monday to Friday from 8:00 a.m. to 4:00 p.m. Patients who are interested in proton therapy will receive a request form to be filled out by him/her or his/her treating physician. Upon receipt of this request form and diagnostically significant preliminary findings, the RPTC radiotherapists will decide, usually within one day, whether proton therapy is a viable option. Once the cost issue has been settled, the patient will immediately get an appointment for medical consultation at the RPTC. If a radiotherapists with expertise in proton therapy confirms the indication for proton therapy in the course of a medical entrance examination at the RPTC, this therapy can be started already after a few days needed for therapy preparation and planning.

 

ACTIVITY REPORT TO MARCH 2012 – THE FIRST THREE YEARS, THE FIRST THOUSAND PATIENTS  

 

Radiotherapy achievements   

 

The key performance parameters of the radiotherapy services offered during the first

three years of operation are presented as frequency distributions in Figures 11 to 14.

  

Figure 11: Number of fractions (= single irradiations) per patient at the RPTC – Distribution (March 2012)

 

Figure 12: Number of fields per patient at the RPTC – Distribution (March 2012)

 

 

Figure 13: Number of scanned spots per field at the RPTC – Distribution (March 2012)  

 

 

Figure 14: Tumor volumes at the RPTC – Distribution (March 2012)  

 

 

Patient treatments

  

Overall, the proton treatment for 1,004 patients was completed at the RPTC until March 2012. Over the last three years, the number of patients has gone up along with our technical and staff capacity. This is shown graphically in Figure 15. If we look at this rate of development in the number of patients in an international context, we see from Figure 16, that the RPTC (black curve) has grown just like other major facilities worldwide. Figure 16 shows the trend in numbers of patients in Loma Linda, Boston, MD Anderson and the University of Florida, beginning on the day the facilities commenced operations. It is worth noting that the pioneering facility in Loma Linda has a shallower slope and the worldwide renowned cancer treatment center MD Anderson, Houston, has been expanded comparable to RPTC. The rising curve of Florida, where a standard scattering system by IBA has been installed, shows that the rapid increase in patient numbers does not necessarily have anything to do with a technological pioneer or prototype situation.

  

 

Patient treatments

 

Figure 17: Different indication groups of the 1,004 patients treated so far at the RPTC in percent. Table 5 shows the detailed list of tumors treated at the RPTC up to now.

  

 

Geographical origin of patients

 

We have steadily expanded our international catchment area in the third year of operation. We have now treated patients from 37 countries all over the world (Figure 18). 

 

  

Precision irradiation using the proton scanning method in respiratory arrest

 

 

The problem of irradiating organs that move with respiration is a challenge even for physicians and physicists in conventional radiation therapy.

 

The options provided by a high-precision technique such as proton scanning at the RPTC (e.g. active breath holding or motion-triggered irradiation during short segments of the respiratory cycle) were so far not sufficiently reproducible or not sufficiently powerful.  

 

The method of controlled apnea established in our house under general anesthesia has demonstrated its practicality, accuracy and patient safety in more than 1,100 treatments since the start of operations, as can be seen in Table 6.

 

The physiological basis of oxygen supply without mechanical respiratory movements was described already in 1908 by Mr. F. Volhard in the Munich Medical Weekly. However, it took another 50 years for their significance for clinical applications to be recognized. Today, „apneic oxygenation“ is a well-established procedure for surgical and interventional operations.

 

During the apnea phase which, on average, lasts 2 to 3 minutes in which the tumor is irradiated, the anesthetized patient remains connected with the respirator; a constant internal pressure in the lung and a constant flow of oxygen into the lungs is maintained. This enables further O2 uptake into the blood which, as always, occurs by diffusion from the alveoli. Thus, oxygen deficiency is ruled out.

 

The continuous monitoring of oxygen saturation in capillary blood never showed any O2 supply problems. The short periods of apnea, achieved as a result of the speed of the proton irradiation method, also does not lead to any clinically relevant accumulation of CO2.

 

The required daily „superficial“ general anesthesias are described by patients as well tolerated, with mild impairment, such as the observance of the fasting periods, occasional throat discomfort and fatigue following anesthesia are common side  effects of general anesthesia and do not cause any stress.

 

Morten Eckermann

  

 

CLINICAL RESULTS

 

Proton therapy of liver metastases

 

The liver is a frequent target of metastases, especially from primary tumors in the gastrointestinal system due to the blood flow from there (portal system).

 

In general, patients with liver metastases require systemic therapy (chemotherapy). However, Radiotherapy is a treatment option that can be offered to patients with isolated or “oligo” sites of metastatic disease within the liver (Reference 3).

 

The liver is an organ particularly sensitive to radiation; to function properly, it tolerates only a low dose. However, since it has a great compensation capacity, partial irradiation can be performed without major clinical consequences. The total volume irradiated plays the crucial role; healthy liver tissue should be involved as little as possible. Proton therapy enables us to achieve the required steep dose gradients to surrounding healthy liver tissue. Proton therapy with its high conformality and dose concentration in the tumor is therefore an ideal treatment option for liver metastases.

 

In the period from June 29, 2009 to March 15, 2012, 23 patients with liver metastases were treated with proton therapy at the RPTC. The average age of patients was 62 years, most patients had a colorectal cancer as underlying disease (Table 7).  

 

In 21 patients (92%), 1 - 3 liver metastases were treated, one patient had four metastases and one patient even 9 metastases. Almost all patients (96%) had previous surgery, chemotherapy and/or radiation therapy (Table 8).

  

The treatment was performed in 1 - 5 fractions. Most patients received 3 treatments with a total dose of 32.7 Gy (RBE) on average (Table 9).

  

Results:

Proton therapy was well tolerated by all patients. In the course of follow-up, no treatment-related side effect occurred (Table 10).

 

After a median follow-up period of 6 months (2 - 24 months), a complete regression of metastases was observed in 65% of patients. In one patient the tumor size remained unchanged (stable disease), in one patient the tumor became smaller in size but was still visible in imaging studies (partial remission) (Table 10).

  

Summary and conclusion:

The first patients treated for liver metastases by proton irradiation at the Rinecker Proton Therapy Center showed an outstanding response and excellent tolerability.

 

It is concluded that proton therapy provides the best treatment option for patients with liver metastases, with the goal of destroying metastases, delaying disease progression and improving survival. Liver dysfunction occurring with X-ray irradiation, even if the dose level is limited, cannot be observed in proton scanning, even with multiple metastases.

 

Alfred Haidenberger, Barbara Bachtiary

 

 

Proton therapy of intracranial meningiomas

 

 

Intracranial meningiomas are tumors that arise from the covering cells of the pia mater.

 

About 85% of all meningiomas are benign (WHO grade I) and – depending on their anatomical location – can be curatively treated with surgery alone. Often, however, due to their proximity to important brain structures (e.g. optic nerve / chiasm), an operation cannot remove the entire tumor or entails serious side effects.

 

About 10% of all meningiomas have, even after surgical removal that appears to be complete, a high recurrence rate (WHO grade II and III).

 

Despite significant advances in neurosurgery, there has been a need and a growing interest in recent years in additional radiation therapy of meningiomas.

 

The effectiveness of radiotherapy in the treatment of subtotally resected or recurrent meningiomas has been investigated in many studies. It was shown that both the disease-free survival, as well as overall survival, has significantly improved (Reference 4–7). Moreover, it was clearly demonstrated that even after a recurrence a repeat surgery in combination with radiation therapy results in an improved local control and survival rate as compared with surgery alone (Reference 6, 7).

 

Proton therapy as a special form of radiation therapy is superior in the treatment of meningiomas to conventional radiation therapy because due to the steep dose gradients it allows the maximum preservation of healthy brain tissue at a high tumor dose and, at the same time, consecutive long-term tumor control.

 

So far 11 patients with intracranial meningiomas were treated at the RPTC. Most patients were female (64%) and the average age was 53 years (Table 11).

  

Many patients were previously treated with surgery (n = 9) and were assigned with a tumor recurrence (Table 12). The majority of the patients had a meningioma WHO grade I (n = 8).

 

Treatment:

Depending on the location and size of the tumor, 5 to 32 proton treatments were applied with a mean total dose of 52.9 Gy (RBE) (48 - 62 Gy (RBE)) (see Table 13).

  

Results:

Patients were on average followed up for 12.3 months (5 - 26 months). In 9 patients (81%), local tumor control was achieved at the check-ups (see Table 14). All patients tolerated proton therapy well. All patients noted temporary loss of hair, which in most patients grew back within a short time. One patient had an ear infection during proton therapy, which under appropriate therapy subsided again.

 

Summary:

Our first results of proton therapy for meningiomas show that proton therapy is a safe and effective treatment for patients with meningiomas WHO grade I and II. We were able to achieve excellent tumor control, comparable to the internationally published results of photon irradiation. In contrast to X-ray therapy, we have observed a significantly lower level of acute and chronic side effects.

 

Recently, the Paul Scherrer Institute (PSI) published the long-term results for treatment of meningioma with protons. The PSI is working with the spot scanning method (however, a simplified version) which is also employed at the RPTC (Reference 8). The excellent long-term results achieved there reinforce our conviction that proton therapy is the optimal therapy for incompletely resected or recurrent meningiomas.

 

Marc Walser

 

 

Locally advanced pancreatic cancer

 

Malignant neoplasms of the pancreas are among those cancers, for which early symptoms are rare and uncharacteristic. Therefore, pancreatic cancer is often diagnosed at an advanced stage in which surgery – which is always fraught with risk and subject to side effects – is no longer possible. The appropriate therapy for patients with locally advanced pancreatic cancer is controversially debated in the scientific literature: There are study results on chemotherapy alone, combined radio chemotherapy, induction chemotherapy followed by Radio/Chemotherapy or radiotherapy alone. So far, a significant benefit for the patients concerned could not be proven with any treatment, so that, unfortunately, at this late stage healing is at present not likely (Reference 9).

 

The role of radiotherapy in the treatment of locally advanced pancreatic cancer was tested in several studies. With modern radiotherapy techniques such as intensitymodulated radiotherapy (IMRT), tomotherapy and stereotactic ARC radiotherapy, it is possible to adapt the distribution of the radiation dose in the tumor area more accurately to the tumor shape. Whatever the X-ray radiation method chosen, however, there is a considerable burden on the organs at risk, such as liver, kidney, stomach, spinal cord and intestines. This forces us to limit the tumor dose, since any further increase in dose in the tumor would be at the expense of the healthy tissue, the risk of side effects would be unacceptably high and, therefore, no benefit is to be expected for the patient (Reference 9–12).

 

With protons, a three times better radiation concentration can be achieved in the tumor, without delivering a radiation dose behind the tumor (as seen in the beam direction). In contrast to X-rays, proton therapy also deposits a lower dose of radiation in front of the tumor. Thus, irradiation of pancreatic cancer with a curative dose is possible.

 

From summer 2009 to summer 2011, a total of 26 patients with inoperable, histologically confirmed pancreatic cancer were irradiated with protons at the RINECKER PROTON THERAPY CENTER – following different pre-treatments (chemotherapy and attempted surgery). Disregarding initial attempts to treat patients, there are 13 patients who received standardized irradiation since summer 2010. 10 patients (77%) were treated with the RPTC standard dosage of 18 x 3 Gy (RBE), in one patient (8%) the dose was reduced due to chemotherapy side effects to 15 x 3 Gy (RBE), 2 patients were irradiated, due to simultaneous liver metastases, with 10 x 4 Gy (RBE) in the pancreas and 3 x 14 Gy (RBE) in the area of the liver metastases in anesthesia (apnea condition) (Table 15).     

  

Results:

During therapy and 6 months after the end of therapy no serious side effects (= grade 3 side effects, such as weight loss greater than 15% or frequent nausea) were observed (Table 16).

 

During therapy, grade 2 side effects occurred in 38% (for example, moderate weight loss less than 15% or moderate abdominal pain), decreased again, however, up to 8 weeks after end of therapy; one patient developed a grade 1 side effect in the form of a slight radiodermatitis. In the period up to 6 months after therapy, only one patient (8%) developed a grade 1 side effect (for example, vomiting once) (Table 16). Biliary disorders after irradiation could not be detected clinically or in the laboratory.

  

Six months after therapy, all patients achieved remission (i.e. a regression of the tumor in MRI or CT scans). That means a local control rate of 100%. In two thirds of the patients remission was even between 60 and 70% of the initial tumor volume (Table 17).

  

Summary and conclusion:

In conclusion, the first results of proton therapy of pancreatic cancer show an excellent efficiency with a local control rate of 100% with very good tolerability. These results encourage us to pursue the concept of proton therapy in the treatment of pancreatic cancer and to offer our patients an effective treatment option.

 

These good results with advanced or inoperable pancreatic cancer also raise the

question whether proton scanning can possibly replace surgery in the early stages of pancreatic cancer. Ultimately, the risk of surgery is high, the number of permanent cures achieved with surgery, however, is low.

 

Alfred Haidenberger 

 

 

Early results with „normal“ prostate cancer

 

360 of our 1,004 patients who underwent Proton Therapy at the RPTC suffered from prostate cancer. 69 of those were high-risk cases which will be discussed in one of the following chapters.

 

At this point we will report about these 291 cases with low and medium risk. Due to the high density of screening tests, most patients fortunately get their final prostate cancer diagnosis earlyThe high proportion of prostate cancer in the total number of patients treated at the RPTC is due to three factors: First, prostate cancer is the most common cancer in men (Reference 13), and it is frequently treated by radiotherapy. Second, the patients often contact prostate cancer patient groups (support groups) who have acquired a lot of expertise. In this manner, knowledge of the benefits of proton therapy has spread quickly. Third, patients will be confronted with a variety of therapeutic approaches from different specialist – urologists, oncologists, surgical urologists and radio-oncologists. Ultimately, all these treatment alternatives from which the patient can choose are more or less fraught with risk.

 

The benefit of patients suffering from prostate cancer – and also the therapist‘s dilemma – is the slow growth of this cancer. Usually, patients die before the disease can take its fatal course: Autopsies in men who died at the age of 65 or older from other causes showed, after examination of the entire prostate tissue, in not less than 75% of the examined deceased prostate cells, which according to all histological histopathological, microscopic) criteria had to be classified as cancer cells (Reference 14). The clinical incidence of prostate cancer in only 9.0% of all men clearly means that most men do not live to see the „outbreak“ of cancer, but die with a „dormant“ cancer. On the other hand, especially the side effects and disadvantages of each therapy must be carefully considered. And this trade-off is difficult. A largescale American study showed that, at least in the United States, recommendations of the various therapists how to proceed differ widely from region to region. One American state, for example, recommended surgery, the prostatectomy, twice as often as the other states. How a patient is treated obviously depends on where he lives and probably also on whether he first consulted an operating or non-operating urologist.

 

Proton therapy for prostate cancer is an alternative to the following treatments:

  • Doing nothing, the so-called active surveillance. This approach is closely monitoring a patient ́s condition without giving any treatment unless there are chances in the test results. The name already indicates the inherent logical contradiction: All available examinations of an early carcinoma of the prostate – palpation, ultrasound, magnetic resonance, biopsy histology, PSA lab results – can offer a static momentary picture, and with advanced forms they can also provide probability statistics of the length of survival. However, they cannot predict the „outbreak“ just as little as geologists can predict the eruption of a volcano. Examinations have to be repeated at intervals; at the onset of the tumor, half of the examination interval corresponds on average to the time lost for early treatment. Rationally, this approach can be considered only if the vital functions of very old patients may be endangered through surgery, or if the known functional disadvantages (incontinence, impotence) are taken into account. Compared with low side effect treatments, active surveillance is hard to justify, because compared to all other treatments it shows statistically a
  • higher tumor-related mortality.
  • Systemic therapy. As a rule, except for final stages which are treated with chemotherapy, this means an androgen deprivation therapy. The slang term „chemical castration“ is undoubtedly exaggerated, but the therapy is also not free of side effects: It corresponds at least to the perimenopausal symptoms in women. Patients with prostate cancer on androgen deprivation therapy experience deleterious side effects, including sexual dysfunction, hot flashes and osteoporosis. Also, the androgen deprivation therapy induces gynecomastia and should therefore be combined with an prophylactic breast radiotherapy to prevent painful swelling of the male mammary gland. In combination with active treatments such as surgery or radiation therapy, the adjuvant androgen deprivation therapy improves overall survival when it is given in the long term: Studies cover up to three years of treatment (Reference 15). The onset of androgen deprivation therapy may be identical with the start of active radiation therapy or surgery. A continuation of the hormonal deprivation therapy is often recommended. In terms of tumor cell statistics, an earlier start of the hormone therapy is hardto justifyif it delays the actual radiation treatment with immediate reduction of the number of tumor cells that may become resistant to therapy or metastasize.
  • Surgery. Patients in good health are often offered surgery as treatment for prostate cancer. Surgery is burdened by the risk of surgery for very elderly patients. All patients, however, are affected by the removal of a portion of the bladder closure mechanisms, leading to partial or complete incontinence (Reference 16). Also, the operation will destroy one, in a radical version both nerves controlling erectile function with the consequence of a loss of sexual function (Reference 16). The probability that this may happen is often assessed very individually by different surgeons. Objective figures can be found in the literature offered, for example, by prostate cancer support groups. The real problem of prostatectomy lies in the relationship of efficacy versus side effects: The efficacy is constrained by the possible presence of already detected metastases – which must then be irradiated – or, worse yet, undetected metastases. Furthermore, not least because of the above-mentioned dilemma: Operations are often ineffective because the onset of the cancer would not have occurred.
  • Internal radiation therapy. The prostate can be pinned with needles through the perineum. We distinguish between permanent and temporary brachytherapy. Briefely, a highly radioactive isotope sealed in needles, seeds, wires, or catheters are placed directly into or near the cancer. Depending on the tumor stage, a very reliable eradication of the tumor is possible with this method. Extremely high radiation doses can be used, which due to the short range of the isotopes used, the applied dose is limited to the prostate. The ureter, nevertheless, tolerates this radiation. The problem is the placement of the needles, which is always much more accurate in the computer diagrams used than in the clinic. The method has its supporters; however, the standard external radiation (teletherapy) has not yet been superseded.
  • External radiation therapy with X-rays or protons. External beam therapy uses a machine outside the body to send radiation toward the cancer. Today‘s modern X-ray irradiation (see also the following section, „High-risk prostate cancer“) is equivalent to surgery (Reference 17) - but exhibits fewer side effects and is risk free. Since the radical prostatectomy is an invasive procedure, it is particularly distressing for older patients and carries higher surgical complication risk. In addition, the rate of the quality of life debilitating side effects such as incontinence and impotence is significantly higher with radical prostatectomy than with radiotherapy. Modern radiation therapy is thus a real treatment alternative that spares patients not only surgery, but also the side effects often associated with surgery. Even more so when irradiation is necessary anyway, even after successful surgery, if cancer has already spread to the lymph nodes.

 

Proton radiation is different from X-ray radiation only in the local dose distribution (Reference 18). This is so crucial because the tumor dose administered by X-rays does not reach the optimal dose level on the curve between dose and safe tumor sterilization effect. The reasons are not of a technical nature, but are to be found in the limitation of the dose caused by X-rays in order to reduce the exposure of the surrounding organs: above all, the rectum near the tumor and the other surrounding tissues, including the hip joints, the nervous pathways and beyond. These limits imposed by the collateral damages of X-ray irradiation do not apply to proton scanning therapy. The older proton scattering therapy which is still employed in Loma Linda, Los Angeles, and at the Harvard University, has caused high-dose regions in healthy tissue in front of the tumor, i.e. in the direction of the radiation source. This is no longer the case with the scanning method practiced at the RPTC. At the RPTC, the ratio of effective radiation in the tumor to radiation damage in the surrounding area is better by a factor of 3 - 5, depending on the anatomy, than with other, even the most sophisticated and modern X-ray equipment. This is the essence of proton therapy.

 

 

Tolerability of therapy

 

The duration of Proton Therapy treatment in our patients is only 21 days with a dose of 3 Gy (RBE) for each fraction (X-ray irradiation at present usually 41). This method is now practiced in Loma Linda, Los Angeles and at the MD Anderson Center in Houston. The tolerance was excellent (Table 18). This means not only increased comfort for the patient who usually remains symptom-free during treatment, without need for hospitalization; moreover, the patient can continue to work without interruption, provided he is not engaged in physical occupations. Also, there is virtually no age limit. The good tolerability also means that the path is open to a higher dose in the target area, in the tumor.

 

 

Treatment results

 

As already indicated, in comparison with X-rays, there are significantly fewer side effects, also during the period following the irradiation (Table 18).

  

The 360 prostate irradiations were carried out after the technical start of the RPTC in 2009 with increasing frequency in the years 2010 and 2011. Given the low growth rate of prostate cancer, this period is too short to publish final results. It is expected, however, that the therapy regimens currently used at the above mentioned institutes in Loma Linda and in Houston will provide a large number of long-term observations over five years in the next five to six years. Currently, only the older results of the facility at Loma Linda, Los Angeles, can be used to discuss the expectations regarding chances for healing. With its scattering method, Loma Linda achieved a slightly worse protection of the surrounding tissue than the RPTC, so that the RPTC will at least match the results of Loma Linda. And these were indisputably the world‘s best with 91.3% five-year cures for prostate cancer stages up to 1b - 2b with PSA <15 ng/ml (Reference 19).

 

 

The future of prostate cancer treatment

 

The clear goal of treatment of each prostate cancer should be to sterilize the cancer, to kill the tumor, without any or only a minimum of side effects. The superior tolerability of proton scanning in our 360 patients showed that there are two ways to achieve this goal:

 

Due to the highrt dose concentration of proton radiation in the tumor as compared with X-rays, the physical dose in the tumor could be increased significantly without reaching even the X-ray standard dose in healthy tissue.

 

The good tolerability in healthy tissue also allows us to reduce the number of individual sessions (fractions) in favor of a higher dose for each individual session. This leads to a higher „effective dose“ at the tumor, because the cancer has less time to recover, that is, to utilize so-called repair mechanisms. The relationship dose/fraction number/ effectiveness can be mathematically estimated relative to the different tumor types and our specifications of the effective doses are based on this estimate. The reduction of the number of fractions from 41, which is typical for X-ray therapy today, to 21, which is what RPTC patients get, is the result of these considerations.

 

The road to a future treatment is long, marked by caution and the intention not to experiment on patients in Munich. So what are the future improvements? The experience we acquired in recent years indicates to us that a reduction of the number of sessions from now 21 to 15 is feasible. With procedural changes, with appropriate licenses and still more experience, a long-term goal could be the reduction to 7 sessions, with a then significantly higher effectiveness of the radiation targeted at the tumor. Then a dose would be reached which in the S-shaped dose response curve reaches levels where all tumor cells are killed with such high reliability that any further increase of the dose would not bring any additional benefit: the desired dose.

 

If in the distant future the vision becomes reality that a common tumor can be eliminated reliably in a single treatment which lasts 15 minutes, is completely pain free and has no serious side effects – then proton scanning will lead the way.

 

Barbara Bachtiary, Marc Walser, Hans Rinecker

 

 

High-risk prostate cancer

 

Every year about 58,000 men in Germany are faced with a diagnosis of prostate cancer. In a majority of these patients this is primarily a still localized tumor growth, which is detected thanks to better preventive check-ups.

 

For these patients, primary radiation therapy is a treatment option that is equivalent to radical prostatectomy. Numerous recent studies show comparable 10 to 15-year data with regard to disease-specific and overall survival.

 

The German S3 Guidelines for „Early Detection, Diagnosis and Treatment of Prostate Cancer“ cites radiotherapy as an equivalent treatment option in addition to radical prostatectomy, and requires appropriate patient education regarding all treatment options. Patients are divided into risk groups according to the tumor stage, the maximum initial PSA level and the Gleason score. The determination of the optimal therapy is based primarily on the risk allocation.

 

In patients with high Gleason score and/or high pre-therapy PSA level, the risk of capsular perforation, seminal vesicle infiltration or microscopic lymph node involvement is increased. In this so-called „high-risk group“, proton therapy offers high tumor control rates with minimal side effects, due to the option of adapting the radiation dose to the target region (additional irradiation of the seminal vesicle region and of the lymph nodes).

 

In the period 11/2009 to 12/2011, 69 prostate cancer patients in the „high-risk group“ were treated at the RINECKER PROTON THERAPY CENTER. The recommended therapy for these patients involves the simultaneous treatment with an anti-hormonal therapy along with radiation therapy. 31 of 69 patients, however, declined antihormonal therapy, because they were not willing to accept the side effects, or there were contraindications against anti-hormonal therapy. Below we will present the results of treatment of this patient group (see Table 19).

 

31 patients had a locally advanced prostate cancer with a tumor stage ≥ T2c. The initial median PSA value was 23 ng/ml (ranging from 2.57 to 71.9 ng/ml) and the Gleason score ≥ 8 (Table 19).

  

All 31 patients received radiation to the prostate and seminal vesicles. The administered radiation dose was 63.00 Gy (RBE) in median (range: 63 to 66 Gy (RBE)) where a single dose of 3 Gy (RBE) was given per fraction (Table 20).

 

22 patients received irradiation of the regional lymphatics, in addition to the prostate/seminal vesicle irradiation. Here the administered median dose was 52.5 Gy (RBE) (range: 48 to 54 Gy (RBE)) (Table 20).

  

Results:

Proton therapy was excellently tolerated: only 5 patients (17%) experienced a slight

burning sensation while urinating or slightly increased urinary symptoms during treatment. These mild side effects improved after the end of proton therapy in almost all patients (Table 21).

 

PSA kinetics is the most important component for the assessment of tumor shrinkage after proton therapy. Usually it takes a relatively long time until the level of PSA in the blood has dropped significantly and reached its lowest value.

 

Prior to therapy, our patients had a median initial PSA value of 22.80 ng/ml. Eight months after the end of proton therapy, the median value was only 5.00 ng/ml (Table 21).

  

In conclusion, our initial results of proton therapy of high-risk prostate cancer provide excellent results with minimal side effects. A comparison with internationally published studies shows that proton therapy using the scanning technology is tolerated far better than conventional X-ray radiation therapy.

 

As compared to conventional radiotherapy, proton irradiation is able to reduce the volume of and also the dose to the normal tissue that is also irradiated; therefore, our patients received a higher radiation dose per fraction with a smaller number of fractions – 21 instead of the 41 that are typical for X-ray treatment. It is believed that shortening the overall treatment time will reduce the negative influence of tumor cell repopulation on the local control, so that the high radiation doses per fraction should be clinically more effective with less „stretching“ over long periods of treatment.

 

We are, of course, aware that the comparison with the large numbers of cases of conventional radiation therapy should be interpreted cautiously because of the relatively small sample size and the limited follow-up period; however, our initial results encourage us to continue our treatment strategy in high-risk prostate cancer patients with this concept.

 

Marc Walser, Barbara Bachtiary



Chordoma

 

The chordoma is a very rare tumor, representing about 1-4% of all bone tumors. It arises from transformed remnants of embryonic structures and is preferentially formed at the axial skeleton although mainly the sacrum (29.2%), the skull base (32%) or spine (32.8%) are affected. The incidence of chordoma is 0.08 per 100,000 population; men aged between 60-70 years suffer most frequently from it.

 

Chordomas are slow growing, relatively radiation-resistant tumors, which spread locally very aggressively and invasively along bones and neurological structures. Because they do not cause pain, one can often find a large tumor at the time of diagnosis, which can hardly be distinguished from the surrounding environment. Surgical removal is then very difficult. If an operation is still possible, complete tumor removal can be achieved in only about 50% of cases and makes subsequent radiation therapy necessary.

 

The tolerance dose (maximum dose) in the area of the spinal cord, brainstem, cranial nerves and the rectum is limited. Since exceeding the tolerance would cause irreparable damage, conventional photon radiation therapy is limited in the treatment of chordomas, despite major advances in modern radiotherapy techniques. Several studies report a 5-year local control rate of only 10 - 40% with conventional radiotherapy techniques (Reference 20 – 23).

 

With proton therapy, a significantly higher radiation dose can be applied to the tumor at minimal radiation exposure to surrounding tissue. Protons are more effective in the treatment of chordomas than conventional photon-based radiation therapy: Studies have shown that proton therapy for chordomas of the skull base, cervical spine and the sacral region provides a 5-year local control rate of 50 - 60% (Reference 24 – 28).

 

Until December 2011, 35 patients with chordoma were treated at the RPTC. The most common localization was at the skull base (Table 22). We therefore have limited the following evaluation of therapy results to this group of tumors.

  

To date, 15 patients with a chordoma of the skull base were irradiated with proton therapy. All patients had previous surgery (Table 23). The median dose, applied to the tumor with protons, was 67.4 Gy (RBE) and was administered in single doses of 2 - 3 Gy (RBE) (Table 24).

  

Results:

Proton therapy was well tolerated: During treatment, only 3 patients had mild headache or difficulties while swallowing. These symptoms subsided completely after the end of therapya (Table 24).

 

The check-up after the end of therapy was performed at 3-month intervals; the degree of tumor shrinkage was determined by magnetic resonance imaging. After a median follow-up period of 22 months, all patients showed tumor stabilization or regression (Table 25).

 

Summary and conclusion:

Our data show that proton therapy offers safe and effective treatment of patients with chordoma of the skull base after previous surgery. Although our follow-up period compared to published studies is still relatively short, our results show an excellent local control rate (Reference 29).

 

 Manfred Herbst, Alfred Haidenberger

 

 

WHAT WE ARE WORKING ON NOW

 

What we still have to do?

 

 

We are continuing our annual reports on system optimization.

 

Our four large irradiation stations (gantries) to treat tumors throughout the body are in full clinical operation.

 

The small, fifth fixed beam treatment room is also ready and at the time of publication of the annual report is undergoing technical testing. This system is designed for the irradiation of very small tumors in the eye. It can also be employed for those rare small brain tumors, which were diagnosed not just because of their displacement properties, but in the early stages of growth because they damaged individual nerves. However, in the four large gantries we have achieved such an extreme beam precision that the use of fixed beams outside of the eye will actually be quite limited.

 

Our experience with 1,000 patients treated has taught us one thing: In order to meet all – at the RPTC very demanding – technical system specifications, we have to collaborate with the manufacturer on a continuing basis. The proton facility at the RPTC is so complex that it cannot be commissioned and operated on a turnkey basis. This is a substantial difference to technically much simpler older X-ray irradiation equipment. We need a very close interaction between a competent operator and – in the long term – the developer and manufacturer of the system. This cooperation will certainly be focused on the area of software optimization. Operation should be simpler; the „excessive monitoring“ of the system which may cause too many brief interruptions, for technically trivial reasons, should be more precisely tailored to the set objectives: During operation, the technology monitors itself with no less than 6,000 parameters, sampled in intervals of a few thousandths of a second. This overly cautious design occasionally leads to technically unnecessary, easily to eliminate brief safety shutdowns, which are disturbing for patient and operator alike. The spare parts inventory is also being improved on an ongoing basis. Manufacturing expertise and technical competence of the operator, hand in hand with the operator‘s growing clinical experience, are the basis of an ongoing optimization process at the RPTC.

 

 

Hyper-precision technology in radiotherapy

 

At the RPTC, we have now reached the goal stated in our last annual report: „Hyper precision“ (see Figure 19). Our proton beam is the one with the world‘s highest targeting precision. The smallest volume of tissue sterilizable in the body – we had stated 10 millimeters in diameter – has now been further reduced in anatomically complex areas such as the skull, approaching six millimeters in diameter. This precision naturally raises the level of expectations for all targeting methods. The targeting method used at the RPTC has been patented by us; it obviously provides the highest accuracy. Finally, in addition to the precise reproduction of the patient positioning for each irradiation session, it is also important to analyze the „braking distance“ for the invading protons up to the Bragg peak of maximum effect in detail. In this manner, it can be ruled out, for example, that changes in intestinal content trigger this braking effect less or more strongly, which could lead to a depth displacement of the effect maximum (Bragg peak) of the proton beam. ProHealth AG, therefore, has also developed and applied for a patent to cover this aspect of our work. The method automatically identifies changes in the braking distance in each treatment session as compared with the preparatory diagnostic CT scan, without any additional diagnostic radiation exposure to patients.

 

 

 

Dissemination of knowledge on proton therapy

 

In Germany, the RPTC has the longest and largest clinical experience with proton therapy for all tumor localizations. We are, therefore, a center for training radiation oncology specialist physicians and medical physicists in the field of „Expertise for Proton Therapy“. We were so successful that we have a large pool of formally qualified doctors for our proton scanning who by now have gained extensive experience in the field of proton irradiation.

 

The rejection of appropriate proton irradiation cases by self-proclaimed „experts“ is regrettable. These are in some cases conservative radiation oncologists who, and this is crucial, do not have any planning software for protons to weigh thoroughly the pros and cons of the processes, as required by the legislature in § 80 of the German Radiation Protection Ordinance. The planning software for protons is now so expensive that its use outside of proton centers is neither reasonable nor possible. Even an experienced radiation oncologist may therefore not be in a position to provide a correct indication, or to do a correct comparison of the therapy services offered by his conventional X-ray unit and a proton facility. We hope to raise awareness of these problems with our colleagues.

 

 

Irradiation of the female breast

 

Here we have failed so far. Experiments have been carried out regarding the – in our view absolutely essential – positioning control prior to each irradiation session by means of laser-based surface scanning. Obviously, however, there appears to be no real market for these devices; our business partners have discontinued the production. So we carry on looking for a solution. We will offer irradiation of the female breast only if our precision requirements can also be met for the positioning technology.

 

 

COST COVERAGE BY PUBLIC AND PRIVATE HEALTH INSURERS

 

The RPTC has a constant „order backlog“ of about 150 patients with an indication for irradiation – which, with cancer, is always urgent; however, the confirmation of cost coverage by both public and private health insurance is pending. From a medical point of view, the administrative waiting and decision-making times are often far too long. Health insurers require cost estimates which, however, can be prepared accurately only after complete and complex target planning. In some cases, the coverage decisions are made only after consultation of further organizations such as the independent medical service of the health insurers or external consultants. Consultants with expertise in proton technology, however, are not available; much less are there any computer programs that exactly indicate the differences in treatment between proton scanning and X-rays. Overall, far too many coverage decisions are still delayed individually and it is often debatable whether they were processed correctly. We, therefore, try to obtain faster and more reliable cost coverage procedures in our negotiations with health insurers, which are not always easy, as health insurers in general tend to limit their spending. We have ongoing discussions with several private and public health insurers; these comments may therefore be obsolete at press time. For the latest information please visit our website (www.RPTC.de) wiedergegeben. Here‘s an overview:

 

 

Public health insurance

 

We have concluded pioneering agreements with the AOK Bavaria already before clinical commissioning. The resulting collaboration is excellent and based on trust. Patients insured with this company do not experience any delays caused by case-by-case reviews: The AOK Bavaria assumes full compensation for proton therapy in accordance with the terms of our agreement. Since this agreement provides for a lump sum payment, there is no need to submit time-consuming cost estimates.

 

We are grateful that the AOK Bavaria also serves as a clearinghouse for the many other smaller regional AOKs. These regional public health insurance companies have reservations, independent of the proton therapy, regarding patient treatments outside of their region. The transfer to Bavaria often works smoothly with the larger health insurers (Baden Wuerttemberg, Rhineland-Palatinate, and others). Smaller AOKs located in a greater distance with few members and, therefore, fewer cases, sometimes delay cost coverage or, unfortunately, even reject it in individual cases. Together with our AOK Bavaria partners we work hard to improve the processing of these patient transfers to Bavaria.

 

In Germany there are well over 150 other, often very much split up, public health insurance companies (the number is decreasing due to mergers or, in individual cases, liquidations of smaller health insurers). Discussions with the aim to reach an agreement on time-saving lump sum compensation with the group of Vdek insurers have, unfortunately, not yet led to any positive conclusion.

 

Company health insurance funds are organized outside of these organizations. Under a framework contract with the Bavarian Association of Company Health Insurance Funds, the members of several, in particular larger company health insurance funds close to Bavaria also benefit from faster cost coverage decisions. We are currently working on a realignment and adjustment of these contracts. Again, the goal is standardization.

 

 

Private health insurance

 

In 2011 we made a significant step forward in our negotiations with health insurers regarding cost coverage for proton therapy. We look forward to a cooperation agreement with the Deutsche Beamtenkrankenkasse (German Health Insurance Company) (Debeka), Germany‘s private health insurer with the largest number of members. Debeka health insurance is the first private health insurance company in Germany to conclude an agreement on reimbursement for proton therapy at the RPTC. This contract ensures that Debeka members with cancer, who have an indication for proton therapy, will get medical care at the highest level. This gives the 2.2 million fully insured (including beneficiaries of the aid) access to this gentle and effective method of cancer radiotherapy at Europe‘s most advanced proton therapy center. We are pleased to have with Debeka another strong and competent partner on our side in the fight against cancer.

 

We are in discussions with several other private health insurers; the vast majority of those currently still offers individual cost coverage, which only in part are processed without delays. Of course, we will try again to sign a standard contract with as many health insurers as possible – with the clear objective to save time for the benefit of the patient.

 

We would like to make sure that patients, regardless of whether they hold public or private insurance, do not have to make payments in advance, which happens sometimes, and then even have to take legal action against their cost carrier. To our knowledge, these trials end, almost regularly, prior to jurisdiction to the detriment of the insurer, with a last minute settlement in favor of the patient.

 

 

The GBA

(formerly the Federal Committee of Physicians and Health Insurers)

 

The GBA is a legally established organization where representatives from insurance companies, hospitals and physicians decide, on an equal footing, on the economic efficiency of new treatment methods. These decisions are relevant to the cost coverage for members of public health insurers. After several years of work, the GBA, with the help of analyses by the IQWiG Institute (Institute for Quality and Efficiency in Health Care), has denied approval for a few proton treatment processes, i.e. it has recommended that public health insurers do not cover these costs.

 

This approach is limited on two sides: a ruling by the Federal Constitutional Court commits public cost carriers, in exceptional cases regardless of the discretionary decisions of the GBA, to reimburse the cost of treatment, including proton radiotherapy, when there obviously are no alternative promising treatments. Of course, this applies to approximately 25% of our patients, where previous X-ray irradiation was unsuccessful or not feasible, and no other alternatives were available. The GBA has responded to this Federal Constitutional Court ruling of December 6, 2005 by drawing up a set of exemptions.

 

Another problem with the cost limitations imposed by the GBA is that these limitations are obsolete: Recent international studies on the effectiveness of various proton therapies could not be taken into account in the former discretionary decision, so that these decisions formally run the risk of being ineffective. Our contracts with public health insurers excludes provisions of the GBA „disapproval“.

 

 

Sozialgesetzbuch (Social Code Book) V §§ 116 b, b II, b III.

 

From health care to no care. The initial idea of the original section 116 b SGB V was to clarify the payment obligation of public health insurers for therapies that can be carried out on outpatients, i.e. on not hospitalized patients, who, however, do not fit into the (outpatient) system of accredited physicians (panel doctors). Proton therapy, with its high level of investments, is a classic example. The contracts should be negotiated between hospitals and public health insurance. Obviously, this usually does not work, with the exception of our contract with the AOK Bavaria. Therefore, further amendment of § 116 b is needed: Now, it is up to the federal states to approve these contracts. Baden Wuerttemberg has done this for the test facility in Heidelberg; the facility in Essen, which is not yet in operation, should be approved accordingly by the state of North Rhine-Westphalia. Bavaria licensed the RPTC for inpatient treatment, but not for treatment of outpatients – which, in the opinion of our legal advisors is unlawful. But that is not all yet: the new amendment to section 116 b of January 1, 2012 revokes this provision again. Now, these decisions are to be made by committees which, you guessed it, have not yet been constituted in Bavaria. The above contracts with the public health insurance are subject to another of the numerous articles of the Social Code Book V (§ 140 a, b). With 150 public health insurance funds in Germany, these contracts cannot really be valid nationwide. The clients of smaller funds are not covered. The result: a three-class health system in Bavaria. You have to wait for the next annual report.

OUR TEAM

 

 

Dina Archibold, Michael Arifi, Prof. Dr. med. Barbara Bachtiary, Katja Balzer, Petra Becker, Dr. med. Christian Berchtenbreiter, Mike Blechschmidt, Ana Bubalo, Susanne Conrad, Dr. rer. nat. Gerd Datzmann, Dr. med. Dagmar Dohr, Tobias Domke, Dr. med. Morten Eckermann, Björn Flesch, Dr. med. Sabine Fromm-Haidenberger, Zeljka Grieser, Dr. med. Alfred Haidenberger, Jeannette Hartmeier, Dr. rer. nat. Jörg Hauffe, Silvia Hell, Prof. Dr. med. Manfred Herbst, Dr. rer. nat. Martin Hillbrand, Marie Horn, Sandra Igiel, Julia Irger, Julia Kinder, Gabriel Kappel, Ralf Klesse, Helga Kocher, Daniel Köpl, Sandra Kolbeck, Katrin Langenfeld, Nora Meise, Olga Meltser, Dr. rer. nat. Martin Moosburger, Cornelia Mühler, Daniel Nietsch, Jetula Nuhi, Omar Orellana, Bastian Pausewang, Petra Penzinger, PD Dr. med. Dr. med. habil. Hans Rinecker, Monika Rinecker, Valerie Rinecker, MSc, Agnes Stautner, Sven Pfeiffer, Florian Pötzinger, Andrea Schieh-Schneider, Sonja Schierl, Stefanie Schuster, Jasmin Schumann, Hanna Schütz, Gabriele Siebenkees, Robert Sternberg, Christian Skalsky, Stefanie Stiede, Mario Terei, Judith Tscheschel, Maggie Vazal, Zilha Vucelj, Dr. med. Marc Walser, Henriette Weigel, Markus Wilms, Marina Wolfschaffner, Tanja Ziegler

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