The researchers want to use gel phantoms that make it possible to increase the precision of dosing and 'targeting' therapeutic radiation at the target areas of the patient's body in order to avoid damaging healthy tissues and critical organs as much as possible.

The scientists working on the invention hope that it will be used by cancer treatment centres around the world. Various hospitals already use this method, but to a limited extent due to the lack of an industrial scale offer.

The main goal of the method is to help oncologists to improve the precision of radiotherapy irradiation, says the originator and main author of the technology, Dr. Marek Maryański, a professor at the Gdańsk University of Technology, head of Division of Materials Engineering of Multidimensional Ionizing Radiation Detectors at the Institute of Nanotechnology and Materials Engineering. He adds that the treatment of cancer is the main goal, but not the only one - radiotherapy is also used, for example, in vascular and neurological diseases.

Dr. Maryański said: “Malignant cancers are the second most common cause of death in developed countries, and of all patients affected by them, approx. 60 percent qualify for radiation therapy. The scale of the phenomenon is huge.

“The problem is that despite the dynamic development of radiotherapy technology, there are still no adequate methods of verifying treatment plans for individual patients. Before a patient receives treatment, oncologists and medical physicists create a plan that defines a 3D cloud of the dose that will be delivered to the patient.”

In radiotherapy (and many other medical procedures), the effectiveness depends on the dose of the therapeutic agent. For example, when prescribing a medicine to a patient, the desired number of grams of the substance per kilogram of body weight is calculated, etc. 

Maryański said: “The same is true here: we calculate the amount of radiation energy per kilogram of body weight. It is expressed in units called gray. Treatment plans must take this value into account, and additionally define a 3D radiation dose map. The map is three-dimensional, because the patient's body is three-dimensional, and the tumour itself is three-dimensional. And for the treatment to work, the tumour must be attacked in its entirety, in all its points.”

He added that although the dose cloud that the patient is treated with should be identical to the dose cloud that the radiation oncologist previously planned for the patient, “here, however, the problem arises.

“How to verify it in order to be absolutely sure that no error is made. After all, an error with a high dose of radiation - and in medicine we use higher and higher doses every year - is associated with huge negative consequences for the patient."

“The therapeutic effect for each cancer cell depends on the dose it receives. Cells live in 3D space and we have to hit each of them. So we have two variables to check: dose and position. Currently used verification methods are still rooted in the past, when such precision was not required. They are therefore based on measurements at a very limited number of measurement points. 

“The doses are determined only at selected points in a given area and on this basis the real spatial distribution is extrapolated. But in these situations we do not know what is happening beyond the few selected points, or beyond the selected plane. How the actual dose is distributed elsewhere in the tumour - we can only guess.”

He continued: “Our method is different, it guarantees that no detail will escape. Firstly, it detects any possible errors, and secondly, it can help identify their causes so that oncologists and medical physicists can correct them before treatment begins.”

This is where the gel phantoms dr. Maryański's team is working on come into play.

He said: “A phantom is an object that simply represents a part of the patient's body. In general, phantoms contain some kind of detectors (substances or devices) that allow us to measure the dose of radiation absorbed at selected points. But, as I mentioned before, examining selected points is not enough today. We have to measure more precisely, more +densely+.”

The method works as follows: a phantom with a very simple geometry (a ball of the size of a human head) is exposed to the beams of radiation planned for the patient. The phantom is filled with a polymer-gel detector that changes colour and its intensity under the influence of the dose. Then, to quantify the three-dimensional dose cloud, the phantom is placed in a laser tomograph, which - as Maryański explains - works like as an X-ray tomograph, but is much simpler and cheaper to build.

He said: “As a result, we obtain a 3D image, and a number assigned to each point of this image indicates the dose of radiation the point has received. Typical achievable spatial resolution of this method is 0.5 mm, so we will not miss any error.”

For comparison, one of the most valued currently commercially available devices has detectors arranged every 7 mm, in only one plane. 

Dr. Maryański continued: “And imagine that, for example, radiation therapy of a trigeminal nerve disease must focus on an about 4 mm wide lesion. That is smaller than the spacing of these detectors. In this situation, we are not able to determine if we are aiming at the right place. And since the therapeutic dose in the treatment of this disease can be huge (about 20 times higher than the fatal dose for most cells!), there is a high risk that hitting next to the target, we will destroy an important structure of healthy tissue, and the therapeutic effect will be insufficient.”

Verification methods must be accurate, available, inexpensive and fast, because hospitals cannot afford several hours of testing individual patients. At the same time, the doctor and patient must be sure that the treatment will not carry a risk of error.

Maryański continued: “To develop such technology, many different specialists need to cooperate. We work with oncologists, IT specialists, opticians, medical physicists, radiologists, chemists, electronic engineers, mathematicians.” 

His design group, established as part of the 'Polish Returns' grant (funded by NAWA), is currently three people: Dr. Maryański and two research assistants, graduates of the Faculty of Applied Physics and Applied Mathematics, with specialisations in medical physics and nanotechnology. Thanks to the Initiative of Excellence - Research University rector grants, students, including MA students, are also involved in the project. The group also cooperates with the Cancer Centre in Bydgoszcz, the Medical University of Gdańsk and the Institute of Nuclear Physics of the Polish Academy of Sciences that has the only proton radiotherapy Centre in Poland. Foreign cooperation includes three leading proton radiotherapy centres in the USA and one in Belgium.

There will ultimately be two versions of phantoms developed by Dr. Maryański's group. One of them will be permanent, which means that the 'recorded' image of the dose cloud will remain 'forever', as on a photographic film. In the second, reusable version the saved image will stay for several hours and then disappear, enabling re-exposure and reuse of the phantom.

As part of the project, Dr. Maryański also designed and built a laser tomograph. He said: “Initially, I used standard diagnostic scanners for magnetic nuclear imaging to scan gel phantoms. But this did not quite work, because such devices are not able to accurately measure the size of local changes caused by the absorption of the radiation dose; the measuring accuracy of these scanners is far too low for our needs. So we had to find something more accurate. And because the polymers used in our phantom, forming under the influence of radiation, dis[erse light (like sky and clouds), that is, they exhibit a strong optical effect, they can be X-rayed with a laser at different angles, and then reconstructed into a 3D image of +optical density+ with a tomograph.

“The construction of our own laser tomograph turned out to be the most accurate, simplest and cheapest solution.”

When asked whether the results obtained during the phantom scanning perfectly translate into human tissue, the scientist said that this is not needed. He said: “Computers used to plan patients' treatment take into account the differences in external contours and the density of exposed objects with sufficient accuracy and accurately correct the resulting differences in spatial distribution of radiation doses. In a sense, this resembles the brain's ability to correct eye optics imperfections. The unique, missing link in this chain of calculations is the set of densely packed 3D measurement data provided by our method.”

The researcher points out that the system is suitable for verifying treatment plans for all types of radiation therapy: the common photon procedure, and the latest proton procedure, which is potentially much more effective and much more expensive. It is used by relatively few centres in the world, only one in Poland.

The method based on gel phantoms can also be used, for example, to characterize radiation therapy beams with resolution much greater than standard methods and in a much shorter time. This can improve the quality of data on which treatment planning is based.

Dr. Maryański hopes that in the future his solution will be used by thousands of centres around the world. Each hospital providing radiation therapy procedures would be equipped with complete equipment: reusable phantoms, laser tomograph and special software. Thanks to this, verification of treatment plans could be carried out individually for each patient prescribed radiotherapy.

Scanning one phantom currently takes about 40 minutes, which Maryański says is too long. 

He said: “Doctors and medical physicists do not have that much time. Therefore, for now, we intend to offer our solution to clinics in the form of an external audit. It consists in the fact that when a hospital wants to test the strategy of treating a specific disease, for example brain metastasis, it can order verification from us. In this +service+ model, laser tomograph for reading results is not physically located in a given hospital, but remains with us. We send our phantom by courier, medical physicists and doctors in a given facility irradiate it according to the prepared plan, and then send it back to us. We make scans on our laser tomograph, analyse and send results, quantitatively comparing our measurements with the planned spatial distribution of the dose in the phantom.

“This is a temporary solution as long as the technology is still in the prototype phase. But ultimately, once we manage to shorten the time of the procedure to a maximum of 5 minutes, we want to offer it to all centres in the world. And then it will be possible to perform an individual scan of +dose cloud+ in such a gel phantom for each patient.”

He added: “Ultimately, the whole process will also be fully automated; it will not require human supervision. The only task for the hospital employee will be to be arrange the phantom in the right place, and even this process can be highly automated.”

PAP - Science in Poland, Katarzyna Czechowicz

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