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2009-06-01 11:11


Proton therapy for a tumor at the base of the skull

Case report: Proton therapy for a tumor at the base of the skull. On 06/16/2009, we admitted a patient with a malignant basicranial tumor for proton treatment for the first time. The tumor is diagnosed as a chondrosarcoma, originating in the basicranial bone. The 30-year-old patient had previously undergone two surgeries. Each time, removal of the tumor growing toward the brain was incomplete, with subsequent regrowth. From a neurosurgical standpoint, immediate follow-on treatment with proton radiation was highly recommended. Proton therapy represents a promising form of treatment for this disease. Why is this the case?


"A relatively high dose of radiation at the cranial base is required for effective treatment of this type of tumor. The challenge lies in protecting the radiation- sensitive organs adjacent to the tumor such as the brainstem and the ocular nerve, in limiting the high dosage area: a rapid dosage drop from the tumor to the sensitive organs is needed. This is best accomplished through proton beams with a Bragg peak and a sharp marginal drop (see comparative target planning). More than 90% of chondrosarcomas can be cured with proton therapy in comparison to x-ray therapy, which has a long-term survival rate of barely over 20%," according to treating radiotherapist Markus Wilms (photo).

Increasing the capacity of proton technology – a path towards public health care

Proton radiation systems are large and expensive pieces of equipment. The irradiation is complicated and costly (though not nearly as expensive as some competitors claim). Technical optimization is the economical way of making proton therapy the hope of the future. This means increasing utilization rates; that is, the possible number of patients treated by each system.


"We as physicists at the RPTC," says Dr. Gerd Datzmann (photo), "together with the physicians, constantly support the technicians of the manufacturer, Varian Medical Systems, Inc. during the various developmental stages to increase the capacity of our facility toward and even beyond specifications. At present, the manufacturer is conducting related work, for example, adjusting the proton beam control and the certification procedure for our next four radiation rooms, which are already connected to the operational radiation source and software." With our first radiation room in operation, we are obtaining new data and gaining experience with its use in clinical settings, allowing us gradually to optimize the capacity of our system. In Europe, this is pioneering work. Meanwhile we have gained enough experience to have confidence in our ability to increase the system to the planned productivity level when full-capacity operations start. The primary task is updating the software by tuning it. One example:


In our clinical applications, bursts of radiation last only 60 to 120 seconds per treatment field depending on the individual dose and the size of the tumor. Proton radiation itself is painless, but precise targeting requires the patient to remain still. The manufacturer intends to shorten this period; however, in a larger tumor, for example, the beam is magnetically guided through 20 depth layers. The beam reaches up to 10,000 subdivided mini target areas of the tumor. Radiation takes only about 3 to 10 milliseconds per target. At present however, the time needed for switching from depth layer to layer, which requires the redirection of numerous magnets and the beam processing system, is about 3 seconds. By optimizing computer-aided guidance, Varian plans to reduce this time to one second. At least with larger tumors, this adds up to a more comfortable, shorter treatment for the patient and simultaneously to a greater capacity for the facility. While switching the beam from one target point to the next means extremely rapid redirecting of the so-called scanning magnets, the switching of depth layers actually means new electrical adjustment of all guiding magnets in the beam processing and beam distribution – for the first treatment room this are 47, in all other rooms up to 111 magnets. 


Repositioning of the beam from one treatment room to another, in turn, requires complete resetting of all magnets, and at present still takes 100 seconds. This is caused by the fact that magnetic switches cannot simply be set to zero; residual magnetic fields must be compensated for, a difficult computational process. The time factor for this beam turnover is relatively important since the beam changes not only for each new patient, but also jumps from radiation room to radiation room while different fields (radiation directions) are selected. Again Dr. Gerd Datzmann: "Varian has planned for procedural optimizations that reduce the time needed for switching to 40 seconds. The system will meet our expectations in terms of the simultaneous high-quality treatment of many patients."


Expansion of the RPTC performance spectrum

Experiences from the first three months. The official clinical operating approval allows the RPTC system to treat all tumors up to now treated with x-ray radiation. The most recent version of CMS/Elektra therapy planning systems available to us allows us to utilize the therapy spectrum to a larger extent. During the first three months, the following regions and indications were treated at the RPTC:


Cranial and faciocranial (brain metastasis, skull base tumor)

Spine (Ewing sarcoma, metastases)

Thoracic and lung cancer (pleural mesothelioma)

Abdomen (cholangiocellular carcinoma, pancreatic cancer)

Pelvis (pelvic metastasis)

Urogenital organs (prostate cancer, urinary bladder cancer)


Precise and patient-friendly immobilisation

We already reported on the precision targeting system employed at RPTC (see second monthly report). Both for targeting by computerized tomography, and sometimes by combined computerized tomography and MRI, patients are placed in so-called contour beds, which can be adapted to the individual patient, and are used exclusively for a particular patient for all radiation treatment days. In slightly simpler form, these vacuum mattresses are frequently used for the transport of injured patients in emergency situations. There, they are generally referred to as "peanut beds" since their operating principle reminds one of the vacuum packing of peanuts. As long as air remains in the hull, the mattress is soft, fitting the contours of the body. With the air extracted, the material becomes rigid and retains its precise shape, but remains comfortable because it is now custom-fitted. During radiation treatment, the patient is also given a light plastic blanket that is under slight negative pressure. The negative pressure is being monitored automatically. Patient movements that might affect the precision of the radiation lead to immediate interruption of the radiation.


To irradiate the head, we use maxillary molds similar to those used by dentists. These molds, which are attached to a fixture, are also attached to the palate by means of slight negative pressure that is constantly monitored. The molds serve to fix the head in position for millimetre-precision radiation.


According to the head radiology technician Jutta Schreiber (photo) "This allows us to avoid those frightening rigid masks that are familiar from x-ray radiation of the head. So far, we are as satisfied with our immobilisation technique as are our patients. It is much more acceptable and makes the process of radiation, which is itself actually painless, more tolerable than it is the case with conventional devices."


Quality of the pre-diagnostics at the RPTC

Generally, RPTC radiation patients are referred to our facility with a diagnosed tumor, confirmed by microscopic tissue examination. Because the RPTC is also designed to treat patients from far off, it possesses all the necessary diagnostic tools such as ultrasound and endoscopy devices for use in cooperation with the Surgical Hospital Dr. Rinecker.


Regardless of prior outpatient diagnostics, each patient receives a whole body MRI – which is free of radiation and side effects. This procedure scans the entire length of the body, resulting in 300 digital images that can be viewed individually by the evaluating radiologist, or like a film. The MRI allows us to rule out any previously undetected (distant) metastases. On the one hand, this enables us to confirm the patient’s tumor stage; it also provides us with additional treatment options: the proton radiation technique used at the RPTC allows for parallel targeting of metastases (multi-targeting in the scanning system). For suspected metastases, and especially for early metastating tumors like bronchial carcinoma (lung cancer), positron emission tomography (PET) in combination with a CT device (together "PET-CT") is used in addition. In this procedure, the patient is injected with a contrast medium marked with a radioactive isotope with a short half-life in order to identify in a single examination both the exact tumor location (CT) and decide the malignancy of this growth with the isotope, (tumors and metastases exhibit increased metabolic activity). In the same procedure, the patient is guided through a combined computer tomograph and an isotope tomograph (see photo of the system). Computerized tomography "recognizes" the nodule anatomically much more precisely than the isotope method, but without being able to differentiate whether this node is benign or actually malignant. By overlaying both images - the formation in question then can be identified as benign or tumorous.


"Currently, two different contrast mediums with different radioactive isotopes are available for this technology, both have a short half-life, which means that there is little radiation exposure," says Dr. Christian Berchtenbreiter (photo), the head of the Radiology Department, and leading diagnostician at the RPTC. "We order the most commonly used radioactive contrast mediums from the radiopharmacy of the Technical University Munich (Technische Universität München), where it is produced using a cyclotron. Due to the short half-life, our supplier must be close by. In about one-fifth of all cases, however, it would make more sense to use a contrast medium with a different isotope. This could be produced there as well. Unfortunately, the approval process pursuant to the German Drug Law is too cumbersome for the approving authority. Because of this, it is still not possible to market this second isotope, but not out of safety concerns. Unfortunately. Otherwise, diagnostics, which is ultimately concerned with making sure that no parts of the tumor are overlooked, would in many cases be even more accurate in Germany.


Development of the treatment numbers during the first three months. The number of patient inquiries to the Call Center (phone: +49 (0)89/660 680) rose to 3,005 by the end of June.


The RPTC has five treatment rooms, with one room reserved for eye and special head treatments. These treatment rooms are being completed in succession by the manufacturer and turned over to us. Since March 2009, the RPTC has been operating the first of these treatment rooms. Unfortunately, we are only able to treat patients during a limited period of each day as a result of these parallel works , in particular because clinicians and medical physicists perform a precise and extensive validation of key data of the proton system as part of routine clinical practice in order to obtain data for further optimization of systems and processes, and to document the achieved level of quality. "The results of the clinical quality assurance during the first months of operations at the RPTC fully meet our expectations, so that we were able to improve our clinical processes. We will continue to optimize these processes in order to increase the amount of time available for patient treatment," says Board Chairman Dr. Jörg Hauffe. In this early phase, the rates of system utilization at the RPTC already demonstrate a high rate of consistency for such a complex facility (diagram of usage times).


"Over the first few months of operations, we have been able to continuously optimize the still limited usage rates. Our concept of consistent improvement in output coupled with capacity increases has thus been shown to be successful," says Friedrich Rettenberger, the CFO of ProHealth AG. Treatment capacities at the RPTC will be expanded parallel to the completion of the additional treatment rooms by the time the entire facility is completed by Varian in 2010. We have already seen a significant increase in output during the initial months of operation (diagram of treatment capacity).

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