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The ICTR-PHE Blog by Fabio Capello

Monday 27 February

Tuesday 28 February

Wednesday 29 February

Thursday 1 March


Let the challenge begin

On a sunny Monday, the first session of the ICTR-PHE, the five days conference on physics for health and radiation oncology, opened this morning at the International Conference Centre in Geneva. In a crowded room, physicists, biologists and medical doctors are gathered to develop collaborations and synergies that will lead to a global strategy for better healthcare.
The opening of the first day saw CERN Director General Rolf Heuer addressing the audience, to greet the hundreds of scientists coming from all over the world. Their aim, to find a way to share information and understand the needs of each field of study, in order to optimise efforts and resources, and to define a common roadmap.
What are the known effects of radiation on cells? How can we choose which ions are the most suitable for treating cancer? Which innovative technologies are most useful? How can we use the knowledge we already have in each one of these fields and the existing facilities, to help medicine and physics to come to a synergic collaboration? These are some of the issues the first speakers try to address. From the point of view of the physicians, the main goal is to find a better way and to develop and research new ways to deliver in a most effective way the energy inside these particles. Biologists underline the effect of radiation on human tissue, and the need to improve the damage on tumour cells avoiding the damage on the normal tissue
Some open questions remain, said Dr. Alejandro Mazal “What to treat, which kind of cancers, what expenses, which facilities, where, who, in which countries, who is going to support these projects”
Besides, the horizon is wider than it appears. The research could lead to a better understatement not only of the strategies involved in the fight against cancer. Also other fields are involved, such the one related to the space exploration or the protection against irradiation related to human or natural activities.

Beams from outer space

When you think about physics in medicine, the first conclusion you could come to, is of its application against cancer. The range of applications, though, is much wider, and can go straight to the centre of our imagination. In the ICTR-PHE conference, started today in Geneva, the space exploration takes centre stage.
“Ions that burst from the sun could result in an acute irradiation of the crew. It means an augmented risk for the astronaut employed in long term missions to contract potential deathly diseases.” said Uwe Schneider. Which in other term means cancer, a not irrelevant limitation of space exploration and exploitation, which shortens the life-expectancy of the cosmonauts. Question is, how can we protect the crew, or estimate the risk due to the cosmic irradiation, also using this information for some more terrestrial purpose.
The outer space is a constant source of high energy radiation, most of it coming from the sun. A manned spaceflight, and long term missions as the man back to the Moon, or the man on Mars, have to consider not only the technical problems related to the mission itself, but also the ones in terms of protection for the crew.
The exposure to cosmic ray has to be considered from each point of view, underlines Dr Schneider. Age and length of exposition are crucial to determine to which kind of risk the cosmonauts are exposed to. Also a correlation with age, sex and life-expectancy was found. “Purely in term of health related risks, it seems it would be better to send in the outer space an old male astronaut, rather than a young lady.”
Nevertheless, the studies of the effect of the cosmic irradiation on human tissue do not involve solely the space exploration. A comparison between the kind of radiation the astronauts have to stand, and its effect on the human tissue, could help o better understand how these emissions could be used for therapeutic purposes in the fight against cancer.
Again the stars above do not hit only our imagination. Another small step up there, in fact, could lead to some other giant leap. For physics, biology and medicine, and hence for mankind.

A look to the future

The second session of the ICTR-PHE discussed the new pathways explored in the last years for the treatment and the diagnosis of the tumours. In an extensive overview, the researches presented which are the most interesting molecules being investigated, and what are the advantages and the disadvantages of each of them in terms of economical and clinical applicability.
Some kind of tumours that cannot benefit from traditional radiotherapy, or those patient that are not suitable for the protocols we have at the moment, explained Dr Zalutsky, can benefit from these new isotopes.
Although some of them look very interesting for their accuracy in reaching the target while avoiding collateral damages on the normal tissue, the cost or the need for complicated technologies limited their use so far.
The discussion thus moved onto the production of molecules. Implementing the technologies required to produce the isotopes needed for this new therapeutic approach in neither trivial nor inexpensive. This could be a limiting factor both for therapy and for diagnosis.
99mTC is one of these isotopes, and it is used in almost 80% of the diagnostic imaging procedures. Its supply need to be granted to avoid a shortage that could short-circuit the medical imaging process. At the moment there are several projects to bypass this problem. Some involve the creation of new reactors, while others are accelerator based.
“Other ways can be explored.” Said Dr Stora. “Almost 90% of the protons produced by ISOLDE at CERN get wasted. A new project allow us to recover part of the dumped CERN protons and we can use it for the production of medical isotopes.”

Hide and Seek
Together with their application in radiotherapy, those molecules play a leading role in the battle against cancer, as they are a key element in medical imaging. Detection of cancer in the most accurate way leads to an earlier diagnosis and to a better targeting of the tumour. This could significantly improve the quality of life and the survival rate of the patients affected by a neoplastic disease.
Imaging and therapy thus are strictly related. “The goal is a selective irradiation, with the maximum effect on neoplastic cells, and the less possible damage to the normal ones.” explained Dr de Jong. But we want to know where the tumour is to hit it in the most effective way, and the new radioisotopes and techniques researched give us the opportunity to treat a tumour, and to see it at the same time.
Neoplastic diseases are not the only ones that radioisotopes could be used for. Heart’s function and ischemia can be visualized with radio-imaging, assuring results similar to the ones obtained with more invasive techniques. The examination of heart functional conditions versus pure morphology imaging, or the detection of focus of inflammation in the vessels is a plus. “It can be done in very short protocols. 30 to 40 minutes,” said Dr Le Guludec, “with a high diagnostic accuracy.”
Besides clinical imaging, animal models can be of help when a new molecule is considered. Animal are small and their use has several limitations. Nevertheless, the availability of new technologies, as Dr Miederer explained, can help the scientists to go deeper in their studies with a resolution never achieved before. The public opinion though has to be taken in account. “We are walking in a valley of death, if the connections between animals and humans are not clear in our mind.” Dr de Jong said. Furthermore internet produces disinformation. If a research is not conducted in the proper way, its results can be false as well. Besides, that would allow people to consider animal models as a pure cruelty.
Researchers are aware of the ethical issues related with their work. “We can use animal models,” said Dr de Jong again. “But we have to be aware of difference between men and mice. We have like 95% of genes in common. Though, we are different.”

Engineering the future: imaging

Only two years have passed since the last Physics for Health at CERN, but technology seems to have travelled fast. The third session of ICTR-PHE 2012 started today with a broad overview of the new devices and prototypes engineered by different institutions, to improve medical imaging in terms of achieving a better sensitivity with the higher possible resolution.

“In 2010 most of the abstracts presented were related to PET and MRI” Said Alberto Del Guerra, from INFN. “In this conference, most of the topics are related to innovative technologies in medical imaging such the Time of Flight PET or the Hadron Therapy related projects.”

Several projects are under development in the numerous institutions that are actively working in this field, and the presentations this morning covered topics ranging from new solid state detectors, which promise a better resolution both in terms of morphological and functional imaging, to new ideas based on simulation models.

“The Holy Grail would be a detector that could have a spatial resolution of 10 picoseconds.” Dr Schaart said. “The materials and the knowledge that we have at the moment suggest that in a not so far future this goal could be archived.”

Imaging is not only for diagnosis, as some of the speakers explain. Among its roles, there is the definition of the neoplastic mass, needed to correctly direct the beam, avoiding the normal tissues; plus the monitoring of the treatment, essential to evaluate in real-time whether the radiation has been delivered to the tumour in the proper way.

There are different open questions, though. Some are related to the several issues the scientists have to face in order to obtain a properly focused image. There are also the changes of position of the patient, the modifications of anatomical structures, the changes of the target position due to physiological movement, the differences in density as those caused by air trapped in the lungs. These could affect both the diagnosis and the irradiation process. ”Human body is complicated.” Prof Ratib said.

All these possible concerns are being considered, as the numerous abstracts presented this morning underline, and new software and algorithms are currently under study.

The hybrid chimera

How can the combination of different devices and techniques improve treatment and diagnosis? This is one of the main issues that medical imaging is going to face from now on, as technology, along with the development of adequate software, made it possible to combine different imaging systems in the same apparatus.

It was 1994 when CT scan combined with PET was first considered. The very first attempt consisted of a PET scan followed by a CT scan. A specific software allowed to overlap the images, thus adding the data collected by PET to the anatomical details of a CT scan.

“Before that date, nuclear medicine, was more likely unclear medicine, and that was not only due to the swap of the first two letters of its name.” Prof Ratib said. As a matter of fact, the images produced with the sole PET are difficult to decode, because they only show indistinct spots of drug uptake, which cannot be precisely located.

“We knew that the tumour was there, but we had no information regarding its real position. This means that PET alone cannot give enough information to the surgeon or the physician, who are unable to select the proper treatment or intervention.” Which is a crucial point. According to the data presented, up to 50% of the treatment protocol may need to be adjusted after a PET-CT scan. Many patients in fact today receive a correct treatment because of the use of hybrid technologies.

The next ambitious goal is to combine PET with MRI, which offers two main advantages: an amazing  quality of the visualisation of soft tissues details, and (contrary to the CT scan) the absence of patient irradiation, which is especially important in paediatrics cases “You don’t want to irradiate a growing child brain”. Prof Ratib said.

Hybrid technologies are known since almost 20 years, but nowadays we possess the knowledge and technology to develop accurate and innovative devices that can help clinicians to deliver an optimal treatment, thus augmenting the survival chances.

Engineering the future: therapy

Hadron therapy is an option which is gaining momentum in the treatment of human cancer.  Several projects and ideas were presented during the fourth session of ICTR-PHE 2012, aiming at the definition of the key features for an ideal facility.

Marco Schippers reminds the audience that there are many issues to take into account while designing new devices for radiotherapy. Each choice brings to compromise, and the task for scientists is to understand which could lead to the best solution. In other words, the maximum results, with the lowest discomfort for the patient, and possibly at the minimum cost.

From the medical point of view, carbon ion therapy is probably the best treatment at the moment available, but it is expensive. “If you think of carbon ion facilities as the one in Heidelberg, you’re not probably going to build any others. They are big and they are expensive.”, explains Marco Pullia. “But we have several options we can work on.”
As an example, new strategies are being developed, based on well-known technologies, such laser accelerators or cyclotron based gantries.

Humans vs machines

Targeting living tissue means working with mutating elements embedded in a complex environment made of fluids and organs, some of which critical, all part of a whole organism. Such a system is not static. Physiological alterations are always at play, and so are the modifications of its geometry or of its density and pressure. Several issues then arise when therapeutic irradiation is planned.

As explained by Christoph Bert, the displacement of the tumour target during treatment is one of them. “But you cannot think about this motion just as a plain geometrical transformation.” He commented. “Other mechanisms are involved, such the change of beam range or the refraction of the beam itself due to the modification of the target area.”
In other words, it is necessary to carefully evaluate the modifications induced by physiological activities such as breathing.

Different techniques to cope with target motion are already used in clinical practice with good results. The immobilization of the abdomen, made possible with a simple device, helps to reduce the excursion of the chest. Other techniques are more sophisticated, and are related to the way the beam is conveyed and the dose of radiation is delivered to the tumour mass.

A key element is also the tracking of the radiation delivery while the treatment is ongoing, and possibly in real time.
“As the colleagues that have spoken before have underlined several times,” Christoph Bert concluded, “precise monitoring of the treatment is necessary to better define the range, to deliver the higher dose to the cancer, and to minimise the irradiation of the normal tissue.”
All of this highlights, once again, that imaging and treatment are strictly related.

At the end of the day

In a passionate dissertation the Danish scientist Soren M. Bentzen outlined the state of the art of cancer therapy, and how new technologies from different fields as physics, biology, and genomics, can lead to better and tailored treatment.

“One size does not fit all.” reminds Bentzen . Personalized therapy saves lives, and saves money as well. “There are drugs that are extremely effective on a small sample of patients, but they are also incredibly expensive, and no health system can afford to give them to all patients without knowing whether they will respond positively. If we can do a proper screening and identify which patients respond to a given drug before starting the treatment, then we can be also cost effective.”

The role of computing in the treatment protocols and the optimisation of resources was also discussed.
“You cannot make calculations in the old fashioned way. You need a computer to do that.” Bentzen explained. “in the 60s a computer costed billions of dollars. Now a GB is almost for free. This is a revolution.”

Imaging, strictly related to the development of computer technology, is to be considered a revolution as well. Now we can precisely see the tumour mass, and thanks to techniques as PET we can see what the tumour is doing, as well as how it responds to therapy and irradiation.
“But we can do more. With the functional MRI we can see which areas of the brain are related to particular functions as motion or speaking.” Bentzen said. This helps the surgeon to spare important tissue, preserving some functions the loss of which would lead to a poor quality of life for the patient.

Finally, the need of cooperation between different fields of research was highlighted, in the hope that a web of cooperation could lead to a better way to fight cancer.

Challenging the future

What is the future of radiotherapy, and what happens when physics meets biology: the third day of ICTR-PHE 2012 opens with a look onto the future. The new frontiers of therapy and imaging were presented, together with the challenges that medicine has to face in the coming years.

 “The incidence of tumour is increasing. Why? Population is increasing, and so is age. Screening can detect more cases at an earlier stage, which is crucial in terms of treatment and survival rates.” Prof Gerard said. “But the cure for cancer exists. It depends on the cancer, but at the moment we cure a patient out of two.”

The role of cooperation and of data sharing is crucial, as is the use of computer technologies that have dramatically changed the way people can address such issues. Imaging, devices and software development all help to achieve the best results. So do the molecular targets, which use a key/lock combination to bring into the neoplastic cells the active molecules.

Human body is alive, which means that it moves and changes. And it happens every day, explained Dr van Herk. The new technologies allow us to create models that predict the modification of the tissue due to several reasons such as effusion, inflammation, position, eating. This means that we can define the better possible target, delivering the best dose to the tumour and avoiding unnecessary exposure for the normal tissue.

“This is a crucial factor in children. While adults have a low risk to develop a secondary cancer due to RT, in children the risk is 6 times higher.” Explain Prof Gerard. Considering that the expectance of life of a child is different from a 60 year old patient, this is a key issue that physicians and radio oncologist have to deal with.

The aim is to make the patient’s life easier and possibly longer. There are several kinds of disciplines, techniques and field of studies, each one showing innovative perspectives which sometime go even beyond imagination.

“The future is already present” Prof Gerard said.

Computer science and eHealth: the new net

 The future of health depends on research and comprehensive trials. But how can we choose which trials are more relevant, in order to archive the best results, and above all to transfer them into reality? Knowledge engineering is a combination between computer science and academic IT, as Prof Lambin explained in a passionate lecture, and the tools they can bring to researcher have incredible potentials.

“The amount of data we can gather is beyond any human capacities.” Lambin Explained. “Only computer technologies can deal with these data.”

The problem with the current trials, Lambin explained, is that they use very high quality data, but from a few selected patients, which somehow cannot fit reality. Patients all around the world, on the other hand, could provide an incredible amount of data, which would certainly be raw but more related to reality.

“My dream is of electronic data connected.” Lambin said. “That would give updated information every year, or could be used for the automatic selection of patients to put in trial.”

This is one of the aims of the network currently under development, connecting seven institutions in the world such as CATEurope or CAT America. According to expectations, CAT will be able to offer personalised care for each patient, to extract prediction model, to work with machine-readable data.

This could seem a hard task, but according to Lambin the problem at the moment is not technological, but rather related to political, ethic and administrative issues. These can be solved if a common semantic is used. Different informatics systems have to communicate, and this is possible and affordable. Also privacy could be ensured with the use of local databases, which can communicate with a central system.

This huge amount of data could be used for instance to create a virtual patient you can use as reference for trial and researches, merging the information from all the patients that go under imaging and treatment. This would be made possible through the use of electronic Health Record, a paperless way to store and process data.

Results are not virtual. As a recent trial demonstrated, 20% of the patients with rectal cancer could avoided unnecessary surgery thanks to the data comparison gathered from four institute linked to the net. 

Your body matters

Working in vivo is not trivial. Whereas laboratory experiments and simulations show high rate of success once the protocols are applied to the patient, the results could be different from the ones planned.

Human body is alive, which means that it moves, and that changes are happening even over time  intervals of a few hours, explain Dr van Herk.  The tumour will thus be continuously displaced. Many are the factors that influence the displacement of the tumour target: among them, the presence of effusion generated by the neoplastic tissue itself. In lung tumour, effusion could cause the movement of the mass and therefore a shift from the marker used during the treatment planning: this could affect the outcome of radiotherapy.
Other possible causes of movement are the oedema due to inflammation, the variation of the patient position, the change of abdominal pressure related to food intake and the contents of the bowel, the respiration, heart movement, voluntary or involuntary movement from the patients.

Recent technologies allow us to create models that predict the modifications of the tissue and the displacement of the target. This means that we are able to direct the beam in the most accurate way, depositing the best dose to the tumour and avoiding unnecessary exposure for the normal tissue.

Besides, therapeutic irradiation is not only related to tumours. Other diseases could take advantage of it, for example the defects of heart conduction. A wrong irradiation of a live fast moving organ, Dr Packer said, could lead to deathly effects. Targeting needs an extreme accuracy indeed.

The solution is strictly related to imaging. Proper evaluation before treatment, when the planning is made, should be followed by monitoring (possibly in real time) of the treatment, Dr Malinen explained. A post irradiation evaluation could better define whether the dose was correctly given and if the most aggressive area of the tumour were correctly covered.

The existing technologies makes this already possible, as showed by the presentations in the first days of ICTR-PHE 2012. In-room imaging offers a possible solution – as the state-of-the-art presented by Dr Enghardt showed – with the combination in the same location of a device for irradiation and of real-time imaging to track the dose and the distribution of the radiation. A good compromise seems to be offered by MRI combined with new technologies such as solid state detectors.

This is expensive as Dr Malinen showed, but can save lives, and because of its effectiveness it could eventually save money as well.

Different ways, same goal

This morning, some of the key exponents in the fields of biology, medicine and physics gave a series of overview talks covering the newest developments in their respective areas. The session was opened by the German researcher Michael Baumann, who described the role that biology plays in the development of high-tech radiotherapy.

This introduced one of the leitmotifs of the day, i.e. the translation of the findings in biology and medicine, integrated with the research in physics, into a clinical trial and hopefully in the clinical practice. Quality, accuracy, precision are some of the words which were constantly repeated today.  Also the role of the biomarkers, one of the weapons that biology can lend to radiotherapy in the fight against cancer, was highly emphasised.

Two parallel events took place in the afternoon. In Room 2, the important role of the modifications that occur in the cellular microenvironment was discussed. Once again, the presentations underlined the fact that the study of fine biological effects can help to understand why radiotherapy does not always work as it should.

The point of view of the physicists and radiation oncologists was presented in room 3, highlighting the reason why what is reasonable from the engineering point of view, often is not such in clinical applications. In a later session, the technical aspects of targeting and directing beams to the tumour mass were debated.

There was also quite some room to discuss the effects of radiation on normal and neoplastic tissues and to radioprotection, focusing on the needs of the physicians in the clinical practice. The role of genetics and the effects of radiation on vital organs such as the heart or lungs were considered. These studies could help understand why some tumours and some patients do not respond to the therapies, and why some strategies, which on paper look extremely effective, cannot be used in the treatment of patients.

At the end of the day, the keyword is multidisciplinary approach, which is also the scope of ICTR-PHE.

The author

Fabio Capello is a medical doctor, creative writer and medical
editor, with a specialization in paediatrics and a master in
journalism and science communication. He worked in Italy, UK, South
America and Africa. At the moment he lives in Liverpool, UK.