To coincide with World Cancer Day on 4 February, SCK·CEN, the Belgian nuclear research centre, is presenting the results of research work (conducted over several years) into the biological effects on humans of proton therapy compared with conventional radiotherapy. This research was led by Katrien Konings PhD student at SCK·CEN under the auspices of the BHTC consortium (Belgian Hadron Therapy Centre Consortium comprising seven Belgian university hospitals, the Belgian Foundation against Cancer, and SCK·CEN). The results will be presented this Monday at 11 a.m. at SCK·CEN in Mol.
Katrien Konings will defend her doctoral thesis on 22 February in Leuven in the presence of her supervisor Karin Haustermans, professor at KU Leuven and director of the first proton therapy centre, which is due to open in June 2019, and her co-supervisors Marjan Moreels and Sarah Baatout, who work as researchers in the radiobiology unit at SCK·CEN. To coincide with World Cancer Day, she will reveal the main conclusions of Katrien’s Konings’ research.
Currently, the number of cancer patients treated with proton therapy is not growing as fast as it should. Although the physical aspects are well established, numerous questions remain regarding the biological effects of proton therapy, and these have been set out in the recent report from KCE (Belgian Health Care Knowledge Centre). It is crucial that we learn more about the effects of proton therapy on a molecular and cellular level as these effects may differ from those associated with conventional X-rays.
The aim of this research work, which began in 2010, is to compare the effects of different types of radiation in terms of molecular and functional changes in cancer cells. To this end, three types of cancer were studied: brain cancer in children, prostate cancer in men, and breast cancer in women.
Conventional radiotherapy was compared with radiotherapy techniques involving particle beams (hadron therapy using carbon particles or proton therapy using protons). The study focused on the impact of photons and particles (protons and carbon) on both cancer cells and healthy cells. These cells were treated with conventional radiotherapy at SCK·CEN installations in Belgium and with particle-based radiotherapy in the French city of Caen at the institution known as the Grand Accélérateur National d’Ions Lourds (Large Heavy Ion National Accelerator) or GANIL for short, as well as in South Africa at the iThemba LABS research centre in Cape Town.
When a patient is treated with conventional radiotherapy, the radiation affects (within its range) any healthy tissue found in front of the tumour, which it duly passes through before continuing on its way. The most significant damage at cell level is sustained in the tumour, but the healthy tissue surrounding it can suffer considerable damage too.
In the case of particle beam therapy, the intensity of the dose is at its highest when it reaches the tumour. It is as if the dose implodes upon contact with the tumour and does not pass through it. Any effect after that is non-existent. So this new type of treatment makes it possible to use much higher doses – targeted at the tumour – while sparing the healthy tissue surrounding the tumour.
Until a few years ago, everything suggested that the biological effects were practically identical, except for carbon ion therapy, of which the impact is recognised as being two to three times greater. This means far lower doses are required to achieve the same results. So far, there have been compelling indications to suggest that particle beams might also have unique effects. And this is why SCK·CEN and Katrien Konings in particular decided to conduct research into three in vitro cancer models. Katrien Konings studied the effects of particle radiation at both a molecular level (damage to DNA, cell cycle progression and gene expression) and cellular level (survival and migration of cells).
Thanks to this study, it can now be shown that the biological effects of these two therapies, i.e. conventional and particle beam, are also different.
The resistance of a hedgehog
In order to understand the research involved, it is first of all necessary to explain the role of the Hedgehog (Hh) signaling pathway, which is found in the cell and can be activated upon photon radiation. Once irradiated, this pathway becomes active and can make the cells resistant to radiotherapy. In order to neutralise this effect, an inhibitor is required.
During the course of her research, Katrien irradiated cells with photons and added an Hh inhibitor. She then did the same with protons. The results were positive in the case of proton therapy. The cells were less resistant, making the treatment more effective.
“This is only the first important finding of the research we conducted. The second conclusion of the study concerns the migratory effect associated with cancer cells. Particle-based therapies (proton therapy, hadron therapy) associated with an Hh inhibitor have a significant impact on the migratory risk presented by cancer cells. Thanks to this combination, cells become less resistant and migration decreases,” explains Katrien Konings.
10% of patients treated with conventional radiotherapy develop metastases, whereby cells split off from the tumour, take up residence in other parts of the body, and spread the disease accordingly. Stopping this migratory effect ensures that cells remain at the primary tumour site and are irradiated as a result of treatment. The study showed that irradiation with particles reduces the migratory effect, and even more so when irradiation is combined with an Hh inhibitor.
According to Marjan Moreels, a co-supervisor and research scientist at SCK·CEN: “This combination is the only one of its kind in the world. This data shows the potential of particle beam therapy and underlines the fact that medicines targeted at the molecular level look a promising option when combined with particle beam therapy.”
A detailed analysis reveals the most noticeable impact on cellular resistance occurs with childhood cancer, whereas cancer cells in the breast respond best in terms of the migratory effect.
“Thanks to this research work at SCK•CEN in partnership with KULeuven, Katrien Konings has managed to show that particle beam radiation is more effective than X-rays in delaying repairs to DNA damage – with a view to bringing the cell cycle to a halt, reducing cell survival rates, and reducing both cell migration and, indirectly, the associated risk of metastases,“ points out Karin Haustermans, the director of the first proton therapy centre and a professor at KULeuven.
The next phases will focus on analysing the impact of combining radiotherapy with other therapies. Conventional therapy is effective and useful and remains the standard form of therapy. However, in certain cases where X-rays do not work and cells do not respond, it is possible to supplement radiotherapy with other techniques in order to make treatment more effective. Proton therapy is indeed something unique, but it is important to think about backing it up with other approaches – such as immunotherapy and further proton therapy studies in relation to other types of cancer.
Cathy Schoels +32 (0) 0477 68 02 80 - firstname.lastname@example.org