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"One of my goals is to help create a community at regional and national level that will place Spain at the forefront of research in proton therapy and radiobiology".”

The new PI of CiMUS, Yolanda Prezado, joins the research team of this Singular Centre of the USC, contributing a new line of study in which she is already a reference in Paris, proton therapy. The future centre in Galicia, already under construction, means, in Prezado's opinion, a competitive advantage for the Community, since, if properly managed, a facility of this size can catalyse the creation of a strong research community focused on this area and the creation of a pole of reference in the medium term. The USC's CiMUS, due to its resources, professionals, operation and strategic location, is the ideal ecosystem to amplify research in this field. 

New Approaches in Radiotherapy Group - Yolanda Prezado

Photo: Alejandro González García. CiMUS.

For a researcher like you with an extensive career in an international reference centre such as the Curie Institute in Paris, what has led to your transfer to the CiMUS of USC?

The opportunity that Spain has to lead European research in proton therapy, with the ten new centres that are going to be built, one of them in Santiago de Compostela. CiMUS seems to me to be an ideal centre to develop my future research in this field because it offers me the optimal environment to carry out my experiments and expand my research, but also a strategic location concerning the future proton therapy centre in Galicia and the other national proton therapy centres.

What strengths do you find here, what value do you think your group and lines of research can contribute to the current structure of CiMUS, and what objectives do you set yourself in the short and medium term?

CiMUS is an interdisciplinary institute focused on health, with very good researchers and cutting-edge platforms. My team also has an interdisciplinary vision and composition that is perfectly in line with the CiMUS philosophy, but bringing a new subject, radiotherapy (including proton therapy), which also has the advantage of being very transversal, which will allow synergies to be easily established with the different groups.

Bearing in mind that, in Spain, translational research in the field of radiotherapy/proton therapy still has a lot of room for growth compared to other areas, it is a good opportunity to promote these new lines in the country.

My short- and long-term goals are to help create a community at the local-regional and national level, respectively, to place Spain at the forefront of research in radiotherapy/proton therapy and radiobiology.


How do you value the interdisciplinary collaboration between groups and areas of related knowledge, which is so established at CiMUS?

Very positive. It is the same philosophy that we practice in my team and that I believe is crucial for progress in health research. We are in total harmony in this respect.


Specialist in establishing synergies between physics and biology for medical solutions in cancer, particularly in the field of radiotherapy and proton therapy, what potential do you see in CiMUS in this area?

The different specialisations in biology, medicine and Drug Discovery methods at CiMUS are extremely interesting to be applied in the field of radiotherapy.


Director of the "New Approaches in Radiotherapy" initiative, what are these new approaches, what other promising developments or techniques should we be concerned with?

I founded my team in 2013 with the name "New Approaches in Radiotherapy" because it clearly reflects our philosophy. Radiotherapy is one of the cornerstones of cancer treatment. The last decades have seen spectacular technological developments in radiotherapy. However, there are still tumours with a poor prognosis, such as radioresistant tumours. Or in the case of paediatric oncology, survivors still have treatment sequelae.

Our strategy consists of modulating the biological response (and therefore the treatments) by changing the physical parameters of the irradiation. In this line, for example, we have pioneered the development of new radiotherapy techniques, such as mini-beam radiotherapy, which radically changes the spatial distribution of the dose. These new techniques employ very different modes of dose deposition to conventional radiotherapy and lead to a drastic reduction in toxicity, allowing safe dose escalation in aggressive and radioresistant tumours, thus increasing the therapeutic index.

We are also working on so-called FLASH radiotherapy, which plays with the temporal aspects of irradiation and also leads to a certain reduction in toxicity. Other lines of work include the optimisation of radio-immunotherapy combinations and the alliance of radiotherapy and nanoparticles.


What do you think of the future Proton Therapy Centre in Galicia, promoted by the Xunta de Galicia, which will be a reference for the whole northwest of the peninsula, and what will it mean for the field work of your group, and for Galicia?

It is good news that a proton therapy centre is going to be built in Galicia, first and foremost for future patients, who will have a cutting-edge centre that can be beneficial for certain types of tumours. Secondly, for my team, and if the centre is opened to research, it means the possibility of doing some of our research locally, as we were doing at the Institut Curie. If properly managed, a facility of this size can catalyse the creation of a strong research community focused on this area and the creation of a pole of reference in the medium term.   This requires not only the infrastructure, but also clinicians and researchers with experience and international prestige to serve as catalysts.

What other European experiences in proton therapy should serve as a model for us? Why?

I think we should look at facilities such as Manchester or Aarhus that have a beamline dedicated to research and have managed to integrate as part of the centre, or associates, prestigious researchers working side by side with clinicians, also of high level and international prestige.

Proton therapy is presented as a type of "maximum precision" radiotherapy that acts directly on the tumour with little effect on surrounding healthy tissues and organs. In which cases and/or patients is it particularly indicated?

Current international guidelines and recommendations recommend it for ocular tumours, including intraocular melanomas; tumours approaching or located at the base of the skull (e.g. chordomas); primary or metastatic tumours of the spine where spinal cord tolerance can be overcome by conventional treatment or where the spinal cord has previously undergone conventional treatment; hepatocellular cancer; certain types of primary or benign solid tumours in treated children (many in the central nervous system); patients with genetic syndromes that make it crucial to minimise the total radiation volume, such as, but not limited to, patients with NF-1 and retinoblastoma; primary malignant and benign tumours of the central nervous system; cases of re-irradiation (where the cumulative dose to the critical structure would exceed the tolerance dose) and some others.

The indications will expand as research progresses and more and more evidence of potential advantage in other locations is acquired.

You have stated that, among the advantages of proton therapy, it should be noted that proton treatment activates the immune system. Is this the case and why?

There are some indications that protons, but especially heavier ions such as carbon, might be more effective in activating the immune system than conventional X-ray radiotherapy. However, this requires further research.

However, as his group recently published in the journal Nature Communications, anaesthesia protocols in paediatric patients treated with proton therapy need to be revised to avoid cognitive impairment. What are its weaknesses?

Proton therapy is a precise type of radiotherapy that may have reduced side effects compared to conventional X-ray therapy, although not nonexistent. Children undergoing proton therapy usually receive general anaesthesia, supplemented by high levels of oxygen as a safety measure. However, the consequences of changing the oxygen concentration in the treatment had not been studied. In our study, we evaluated the consequences of adding oxygen to anaesthesia in a brain tumour model after conventional proton therapy and a new radiotherapy technique, FLASH proton therapy. We observed that oxygen supplementation leads to more cognitive impairment in both conventional proton therapy and FLASH, with the latter showing the most severe damage. Moreover, oxygen supplementation blocks the infiltration of anti-tumour immune cells into the tumour in conventional proton therapy.

Our study highlights the need to optimise anaesthesia protocols in paediatric radiotherapy to reduce the cognitive impact of treatments, especially those combining radio and immunotherapies.


Are we facing a paradigm shift in cancer research and treatment? Why?

In radiotherapy we certainly are. We are in the midst of a paradigm shift in the speciality. First, because it is evolving from being a technology-driven discipline to a biology-driven one.  And as such, research is becoming more interdisciplinary and more focused on radiobiology and more interfaced with other disciplines such as immunology, genetics, bioinformatics and others. And second, because the scientific observations and results of the last decade are generating a very important change in mentality and clinical practice. For example, there is a growing trend towards hypofractionated treatments (giving higher doses in fewer sessions), which can be beneficial in terms of response and cost of treatment. Or certain ideas considered "heterodox" until a few years ago are increasingly accepted, such as the idea that to eradicate a tumour, strictly homogeneous doses are not necessary.