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01.02.2010

RINECKER PROTON THERAPY CENTER STATUS REPORT: ELEVENTH MONTH OF CLINICAL OPERATION, FEBRUARY ‘10

PROTON-SCANNING – THE ADVANTAGES OF THIS NEW OPTIMIZED RADIATION THERAPY FOR THE PATIENT


THE RINECKER PROTON THERAPY CENTER DEVELOPS TO THE NO. 1 OF PROTON SCANNING FACILITIES WORLDWIDE


With the clinical implementation of the second of our future five therapy stations at RPTC, our daily treatment capacity already increased in part time operation to 40 to 60 patients. Thus, the RPTC currently irradiates more patients using the optimum scanning method than any other institute in the world.

The first centers for ion therapy, regardless if protons or other particles, use the today outdated so-called scattering-method, which is explained below (Loma Linda University near Los Angeles starting from 1991, Massachusetts General Hospital of Harvard University in Boston starting 2001). Some institutes use partial scanning methods (the Paul Scherrer Institute near Zurich in combination with mechanical patient transport, the Bloomington Center near Philadelphia with magnetic deflection of the beam direction, however beam-forming stencils (apertures), the Ion Therapy Center in Heidelberg starting 2010 with fixed beam installations). A fully developed proton scanning technology was introduced for the first time May 2008 at the MD Anderson Cancer Center in Houston. However, only with one therapy station and with, compared to RPTC, a less precise broad beam.

The RPTC in Munich is worldwide the first system designed and optimized for scanning in all four fully movable therapy stations (gantries). Worldwide, all proton facilities currently planned or under construction shall also use scanning technology in the future.

PROTON SCANNING EXTREME: TREATMENT OF A FOUR LITER TUMOR

 

The RPTC was established to introduce the proven form of ion therapy with protons into medical care for all tumors treated until now with X-ray technology. Accordingly, the official clinical operating license issued for this center. Due to this superior radiation technology, extreme X-ray pretreated and ultimately abandoned cases often arrive in Munich.

Proton therapy of a sacral sarcoma with extreme tumor volume. For the first time end of 2009 we treated a patient at RPTC with an unusual large tumor in the pelvic area. The patient suffered from a sacral sarcoma with a volume of almost 4 liters. Only by using proton therapy with scanning at RPTC, a dosage distribution could be achieved, which exposed the tumor to a high dosage, but ensured that hip joints as well as the intestinal area were almost free of exposure (Figure 1). The therapy plan, in other words the computer-aided calculation of proton beam energies and dosages for each individual point (voxel) of the tumor, lead in this case of a tumor of a volume of 3.8 liters (!) to more than 16,000 individual scanning spots divided into 36 depth layers for each radiation field (direction). The computer-generated scanning pattern exhibits a typical meander-shapes structures for every depth layer (Figure 2).

WHAT DOES PROTON SCANNING MEAN IN COMPARISON TO SCATTERING?


At the historical beginning of proton radiation, the so-called scattering method was used. In case of all particle radiation methods the beam generated at the radiation source is always pencil-thick. Transport to the patient has to take place with this diameter as well, as protons only move in vacuum tubes (at RPTC up to 92 m long). However, clinical treatment practice of extensive tumors requires radiation fields of larger dimensions; at RPTC the largest fields reach 40 x 30 cm.


SCATTERING


In case of the earlier scattering method, the beam was scattered to such field dimensions (hence the name).
Scattering filter.

 

An elegant solution would be the use of a magnetic scattering lens (similar to glasses for the farsighted). However, this would lead to a "mountain-like" intensity distribution in the cross-section of the beam (Gauss distribution). Therefore, in case of the scattering method, one or two diffusion disks, e.g. made from perspex, are introduced into the beam, according to the intended field dimension. This ensures uniform scattering across a now circular wide beam cross-section, which is suitable for covering larger tumors.

 


Three-dimensional stencils (apertures).
This conical radiation beam must now be restricted again, shaped to the tumor outline for each of the radiation directions (fields). For this purpose, a similar procedure is used as in X-ray technology, namely stencils with a cutout corresponding to the outline of the tumor. In case of newer X-ray machines this is implemented using electro-mechanical shifting of metal sheets, which are moved to approximately represent the tumor outline, similar to a sideways shifted stack of cards. Due to the penetration power of protons, this approach is not applicable here. A metal stencil must be individually manufactured for every beam direction, hence metal must be cut. Furthermore, particle radiation has the advantage over X-ray that it can be targeted in the third dimension as well (see e.g. the Monthly Report April ´09). his is realized by inserting an inner plastic stencil into each ring aperture for each field. The plastic stencil is individually shaped to adjust its respective depth to the rear outline of the tumor. With that the Bragg peak, hence the efficiency maximum of the particle beam, is adjusted via particle deceleration to the layer geometrically corresponding to the rear tumor circumference.

Depth adjustment. In other words, we now have a selected layer of maximum beam efficiency, i.e. of the Bragg peak, conformal to the rear circumference of the tumor. In order to distribute it to the forward part of the tumor, this layer (Figure 3) must now be swept forward. This is achieved by an additional deceleration filter, usually a wheel (flywheel) featuring perspex segments of different thicknesses. It is rotating at a right angle to the beam and decelerates the beam according to the disk thickness passed through. It practically shifts the efficiency maximum along the third dimension towards the front of the tumor.

Disadvantages of the scattering method. Although this sounds complicated mechanically, this scattering method was fairly easily realized by manufacturers. However, it does have plenty of disadvantages for patients. Nevertheless, the scattering method can achieve a dosage distribution superior over X-ray. However, if compared with scanning, the method is not competitive anymore for larger tumors:

  • The so-called apertures must not only be manufactured for each patient, each tumor, but also for each beam direction (field), and must be exchanged during the treatment sessions. Manufacturing of 3D stencils is realized using computer-controlled milling sequences based on CT scan images of the tumor. An additional effort. The flywheels are usually taken from a stock of more or less fitting examples. However, the exchange usually requires moving gantries back to the basic (zero) position for loading of the new stencil, which unreasonably extends the time the patient has to spend in the gantry. In generally, this triggers the tendency to sub-optimally treat patients using fewer beam directions.  
  • The scattering filters in particular, but also the 3D stencils and flywheels are in the path of protons moving at high speed (of up to 180,000 km/sec). When these particles pass through matter, they are not only scattered and decelerated by the electron shells of the atoms, but they also hit - even though rarely - atomic nuclei, from which they knock out neutrons. This causes the generation of neutron radiation, which does not only spread spherically, but in a fair amount in the direction of the patient. It has been calculated that this neutron dosage reaching healthy tissue of the patient amounts to approx. 0.5 % of the tumor dosage. However, this cannot be neglected, as the patient's health and immune defense for sure will not improve by such additional radiation: The letal overall dosage amounts to only 5% of the common tumor dosage! Scanning methods avoid this risk and exposure.
  • In general, tumors have distorted spherical or lump-type shapes. Adjustment of Bragg peaks to a layer geometrically conforming to the rear contour of the tumor using stencils and their forward shifting by using flywheels, transitions this formed layer in direction of the front contour of the tumor (Figure 4). A side effect of this transition is a frontal projection of the maximum tumor dosage and “overshoot” ("rabbit ear like"). Along with the fact that mechanical parts insertions into the beam path always exhibit inaccuracies, this means that in comparison to the scanning method, the scattering method is the less capable to achieve an optimal and precise dosage pattern, the larger the tumor dimensions are. In other words, healthy tissue is unnecessarily exposed by scattering.

 

SCANNING


The optimized proton scanning technology. In case of the scanning method, the beam  delivered to the therapy station is again only pencil-thick. However, it arrives now in accurately sequentially adjusted particle speeds, which define the individual penetration depths (3 dimensional targeting). In the proximity of the patient, the beam does not receive any deceleration caused by matter contact and leading to neutron radiation: no-touch technology. The beam rather passes two magnetic fields, which deflect it in two dimensions up/down and left/right, similar to old television sets with video tubes: The beam consists of (positively) charged particles, which can be laterally deflected using magnetic fields. (This could be compared to (negatively) charged electrons in case of television, just reversed.) Due to the 1,835 times higher proton mass (which due to its approximation to the speed of light has relativistically increased by up to 25%), the scan magnets of each gantry at RPTC weigh around one ton.

Similar to the function of a television set, the beam meanders across the tumor (Figure 5). However, we here are dealing with a three-dimensional object. Scanning in the third dimension, the depth of the Bragg peak is realized by the already mentioned, simultaneous careful stepwise adjustment of the particle speed and thus the penetration depth of the Bragg peaks (Figure 6).


As you can imagine, the complexity to electronically control the magnets and the radiation source is significant, especially as Einstein's special theory of relativity must be considered due to the relativistic mass increase of fast protons.

Proton scanning advantages for the patient.
The immense development effort of the electronic control was a significant disadvantage of the scanning method, and delayed its worldwide introduction. Commissioning at the RPTC was delayed by this as well. However, these were all disadvantages for the manufacturer, not for the patient!

  • Radiation treatment can be performed faster, as all beam adjustments from field to feild can now be electronically effected while the gantry is rotating. Mechanical parts changes are not necessary anymore. Radiation therapists have more freedom to select even more complex access paths for the beam.
  • The patient will not be exposed to any significant outer neutron radiation. In patient proximity, the beam has only passed through extremely thin-walled measuring chambers and a thin foil, which covers the vacuum transport tube.
  • However, the crucial advantage is: The maximum tumor dosage (remember the frontal scattering projections) does not occur in front of the tumor anymore. With up to more than 10,000 overlapping individual points - see the case example above -, the tumor is accurately radiated within its rear, sideways and front outlines. A better local dosage distribution than that is not conceivable. In fact, the therapist can freely optimize the dosage point by point within the tumor and its surroundings (spread).


Does this new scanning method carry risk potentials for the patient? The answer is a clear no. The key lies in the dosage measurement of each individual radiation point (so-called "spots") located (depending on the tumor depth) e.g. only 5 to 6 mm away from the next radiation point – in order to achieve a uniform dose overlap. Therefore, contrary to a scattering system, the scanning system at the RPTC can be measured and verified point by point. Precision and accuracy of dosage reproduction are impressive (Figure 7). This single point measurement enables the improvement of the current 1 mm accuracy of the radiation precision to an almost unbelievable 0.25 mm, which cannot be matched by any other method (see Monthly Report December ´09).

Occasionally claims surface that compared to scattering methods, scanning methods are more sensitive to patient movements or organ shifts. However, this is not correct. At the tumor borders, both methods display the same sensitivity to target shifts. This is exactly the reason why with both methods experienced physicists and radiooncologists always select a target region larger than the tumor presented by CT scan or MRT. In the case that the target organ is shifting, both methods are also sensitive to over or under dosage within the tumor: The scattering method shifts the Bragg peak (with a frequency of approx. 160 Hertz) back and forth in the depth dimension (z) as well. In case of scanning systems, three spot to spot movement frequencies of the Bragg peaks (by order of magnitude) occur: 0.1 Hz along the z-dimension,  i.e. the penetration depth from scanning layer to scanning layer, 5 Hz from row to row (x, i.e. from left to right) and 100 Hz corresponding to 10 ms, from spot to neighboring spot (y, i.e.  from top to bottom) These scanning frequencies partially match the order of magnitude of the movements of the pericardium (1-2 Hz) and the pulsation of the larger vessels. Physicists and radio oncologists will consider that in the selection of the radiation direction (left/right). Breathing movements of lung and liver must be suppressed for any really precise radiation treatment method (see Monthly Report May ´09).

The RPTC introduces an additional precaution against tumor-internal dosage variations, the so-called repainting. This means that the scanning process is repeated several times, especially in the rear area of the tumor, as in the front area dosage overlap occurs from deeper layers anyway. The spot by spot measurement of dosage points will be maintained during these repeated scans. We know exactly, which dosage we radiated where and can document this individually for each patient.

Scanning is the safe choice.

PROTON SCANNING AND KEY WORDS


The American industry is the world champion in inventing suggestive slogans advertising the advantages of their products. Lately terms have been introduced into radiotherapy not necessarily helping to clarify much. Therefore, here a small glossary for your convenience:

IGRT, Image Guided Radio Therapy. Some time ago, the tumor position was mainly found via orientation points on the body surface. A method, which is not remotely sufficient for modern methods, especially ion therapy, or any particle radiations, which due to the Bragg peak must aim in a three-dimensional space. For particle radiations, not only the exact tumor location in the depth of the body needs to be known, the computer tomogram prepared beforehand also allows to exactly calculate the proton speed braking effect induced by tissue in front of the tumor, and so determining the Bragg peak depth position. The computer images prepared beforehand are also used to verify the patient position, and thus the position of the tumor within the gantry. At RPTC, this is implemented by "locating" the bone environment to the nearest millimeter, as recorded by a diagnostic computer tomogram, by X-ray devices integrated into the gantry. For further details, please refer to Monthly Report April 2009. The RTPC system even allows for verification of the location precision during short radiation breaks throughout the irradiation as well - "image guided radiotherapy".

Other methods try to transport the patient from a preparatory CT to the radiation device as shock free as possible (Paul Scherrer Institute, Villigen). Of course it does not make sense to repeat this procedure in the middle of the irradiation. This basically just assumes that no shifts occur during transportation; it requires a high immobilization effort.

Cone Beam CT. This term describes the integration of a CT scanner into the gantry itself. This is not as complicated as it sounds. If you rotate the gantry around the patient, then it is possible to electronically reconstruct the digital X-ray images at the RPTC like a computer tomogram as well. However, this would mean that during the daily repeated radiation sessions, the radiologist tries each time anew to identically verify the often low-contrast borders of the tumor. In any case, the quality of a Cone Beam CT is inferior to an optimized computer tomography apparatus. Practicality is not much.

Marker. If it is possible that the organ or tumor to be irradiated may shift from day to day relative to the skeleton, then the tumor, e.g. the prostate, can be injected with small golden beads. Then the RPTC targeting system generates a so-called region of interest around these beads and thus verifies the tumor position independent of the surroundings.

IMRT, Intensity Modulated Radiotherapy. In case of conventional X-ray therapy, the geometrical conformity of the radiated target region to the shape of the tumor improves the more radiation directions are used during therapy. Here it makes sense to partially (locally) reduce radiation intensity in some radiation directions, which touch organs at risk. This approach is called Intensity Modulated Radiotherapy. This method naturally further reduces exposure of organs at risk and simultaneously tumor dosage conformity. However: IMRT could not solve the crucial problem of X-ray radiation: The ratio of dosage integrated in the tumor to the dosage integrated in the surroundings, physically caused by the exponential dosage drop of the X-ray in the depth of the body, could not be improved. Dangerous single radiation directions are replaced by something described (by particle treatment specialists) as "dosage bath".

IMPT, Intensity Modulated Proton Therapy. This term originates in scattering systems. In the case of scanning systems, each individual tumor region, each so-called "spot" or "voxel" is always irradiated with a singularly adjusted dosage, individual dosage modifications are routinely planned. The dosage is individually optimized spot by spot.

Active Scanning. This fairly meaningless term is currently popular for the method we have described here in detail: PROTON SCANNING.



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