Cancer therapy: millions for ions

5. August 2014
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The irradiation of tumours using charged particles is much more effective than that using X-rays. In view of the high costs however, the procedure probably finds its way onto the list of options for only a tenth of all cancer patients. Therefore there exist doubts: is ion therapy a technology for the future?

Investing as much as 200 million Euros for radiotherapy on rare tumour types? Does it make sense? Employees of the Heidelberg Ion-Beam Therapy Centre (HIT) would certainly answer this question without hesitation with a “yes.”

Loaded carbon

Germany and Japan, which has four facilities of this type, are considered to be leaders in this technology. Worldwide, according to expert estimates, around 100,000 patients have already been irradiated with “heavy ions”, which are even more appropriate than protons at striking the tumour effectively but at the same time preserve healthy tissue as much as possible. In Europe there are numerous proton radiation centres. The choice of being able to shoot fast charged carbon atoms has until now been offered in three places: aside from Heidelberg there are Italy’s Pavia and Japan’s Hyogo. In Germany so far about 1,500 patients have undergone treatment in the centre completed five years ago – according to current studies with a high success rate. Here, the radiation therapists under the direction of Jürgen Debus specialise particularly on tumours on which other radio-oncological treatments fail or excessively damage healthy tissue.

Deadly double-strand breaks

Together with the size of the particles that hit the tumour, their destructive power increases. At the large ion irradiation facilities, ions reach 70 percent of the speed of light upon their exit from the accelerator loop. In contrast to photons, which immediately release their energy upon hitting an obstacle, ions go like a sharp knife along a narrow beam path through surface tissue, putting their energy out only when they are almost at a standstill. This so-called “Bragg-effect” makes it possible to target the tumour with precision – without excessively damaging the surrounding tissue. Unlike using a normal X-ray gun, the heavy mass of carbon ions causes a high rate of double-strand breaks in the DNA of the target tissue. If these fractures occur on adjacent sites of the double helix, even an effective repair system of tumour cell would hardly be able to piece the individual sections of information back together again and enable the cell to survive.

A major advantage of ion beams is that they also lead cells to die where other irradiation methods fail: in hypoxic regions of the tumour. Many anti-tumour weapons need the help of oxygen free radicals to get lethal reaction mechanisms in the cell going. Therefore, regions with low oxygen content are often resistant to radiation. At these locations, after treatment a growing tumour then most likely regrows. The precision of the ion beam allows the radiologists to increase the dose of radiation. Bombardment with carbon ions allows about one-third higher doses than do X-rays, with protons nonetheless an increase of one-fifth is also possible. This for the patient works out as shorter times which the patient needs to spend under the unit. Instead of ten to twenty sessions there often are with this procedure only a few radiation session appointments necessary.

Ion radiation: accuracy spares healthy tissue

In Heidelberg, doctors treat about 750 patients a year, the ion beam is operationally ready around the clock and serves research purposes when no patient occupies the treatment couch. The special feature of HIT is the movable radiation source (gantry). The huge steel structure with a diameter of 13 metres allows irradiation from all sides and thus paves the optimal path for the ions – or optionally, the protons – to the target area. Target accuracy 1 mm, maximum penetration depth 30 cm, the facility data sheet says.

It’s especially in the case of tumours which have sensitive tissue in their vicinity that this elaborate irradiation technique comes into consideration. These are mainly in the head and neck region, but this group also includes some that are far away from the body surface, such as prostate and hepatocellular carcinomas. In particular, it’s children with cancer who are sent by doctors to Heidelberg. The high success rate of this type of irradiation plays an important role in this – as also does the fact that healthy tissue absorbs little harm through the complex radiation process. Development disorders occur less often than with other types of radiation.

Raster scanning: maximum dose for each tumour cell

The developers have been working rather intensively here to increase the efficiency and accuracy of the ray blaster even further. With “raster scanning” the computer sections the tumour as such into 1 mm slices by means of an exact CT image. Depending on the location of these sections, the radiation comes from a specific direction with a precisely defined energy level. Similarly to intensity-modulated radiotherapy, ” the beams fill out the contours of the tumour as the hand does a glove”; this is the technical director of the plant, Thomas Haberer’s, figurative illustration of the technology involved. Depending on requirements, not only are protons and carbon used, but alternatively also oxygen, helium or lithium ions, all having different characteristics in terms of the power output, penetration depth and other characteristics of the beam path. Especially in the case of tumours involving a tissue mix of malignant and normal cells, doctors and physicists can balance out the destructive power of large ions with the finer weaponry of smaller faster particles and make individualised adjustments.

90 Percent success rate

There are still only few ion irradiation facilities worldwide and therefore also only few studies that have been done on their effectiveness as compared to traditional methods. In Japan, the success rate in the treatment of recurrent rectal cancer stands at around 90 percent. In contrast, X-ray therapy achieves only 30 to 70 percent. There, radiation therapists are currently investigating the possibilities of fighting inoperable pancreatic tumours using combined heavy ion and chemotherapy. One study should also clarify whether a neoadjuvant radiation therapy promises success on this type of tumour.

Given these promising perspectives, several new centres are already in the planning or will shortly be ready for opening. One such facility in Austria set up following the Heidelberg version should be in routine operation next year, the same is happening in France and China. America is currently restraining itself, but would like to help with a new heavy ion therapy technique in getting things to a lower cost, achieving faster patient throughput and thus further dissemination of the concept. The outcome here is supposed to be that fewer ions come out at very high regularity from the accelerator, thus reducing the high energy consumption of the system. Superconducting magnets produce stronger fields compared to those previously used and could thus significantly reduce the large dimensions of the beam control technology.

Enough patients for economically viable operation?

The fact that not everything which gets planned and is already constructed ends up necessarily as a model of success is made evident by the ion therapy facility in Marburg. With this technique, not as many patients are able to be treated as would be necessary for economic operation. Siemens already last year applied for the disassembly of the operating centre presently running as a trial operation, a few weeks ago the Rhön-Klinikum and the University Hospital in Heidelberg, Germany, decided to annex the facility to the existing centre in Heidelberg and to have it running in standard operation in 2015. Similar utilisation problems are also foreseen by critics with regard to the Austrian irradiation centre in Wiener Neustadt, where government agencies have taken over the financing.

Ion radiation therapy is expensive: annually, operating costs amount to around 15-20 million Euros. The costs of treatment for one patient therefore are in excess of 20,000 euros. In the long term, so hope radiotherapists, about one in ten cancer patient will benefit from a shot of heavy ions. As it is, complicated cancer operations carried out in close proximity to sensitive vital organs are also burdensome in terms of their costs. For treatment using innovative anti-tumour agents, five-figure sums pile up just as quickly. In the area of know-how in the medical use of heavy ions, Germany stands among the world elites. Even the investment of large amounts of money could thus prove worthwhile over a longer period of time.

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Dr Jawahar Ticku
Dr Jawahar Ticku

Proton beam therapy is definitely a very good modality for deep seated tumors. But it may be ionizing radiation or the proton beam therapy, they are only for localized treatment but the problem in cancer is local spread and metastasis in which case both the modalities are useless. Yes they may be useful in very small hypoxic residual disease where chemo agents cannot reach, but such percentage of patients will be very low. So it will again be questionable whether such huge investment is recommonded and how many patients will be benefited by this therapy.

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