Wednesday 17 February

In the morning…

Starting at 8:30 a.m. in front of an already packed room, the lecture funded by the European Society for Therapeutic Radiotherapy and Oncology (ESTRO) gave the floor to Eric Deutsch, from the Gustave Roussy Cancer Campus Grand Paris. During his 30 minute talk, Deutsch gave an overview of the new concepts that impact the understanding of the basic mechanics of oncology, leading to a new perception of the biological response to radiotherapy. Nowadays, direct radiation-induced cell kill of tumor clonogens has to be integrated within the concept of microenvironment: this concept implies the consideration of several cellular compartments, which are shown to contribute to both tumor response and the generation of normal tissue damage. These findings have paved the way for an emerging new generation of combined clinical trials that, we hope, will be presented at the next edition of the ICTR-PHE conference!

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Eric Deutsch receives the ESTRO award from Yolanda Lievens, ESTRO 35 SPC chair. (Picture: Salvatore Fiore)

After this very interesting talk, Ugo Amaldi and Norman Coleman came on stage to chair this morning’s plenary session. They welcomed Philippe Lambin, from the University Medical Centre of Maastricht, who described how distributed learning can be the solution for rapid learning health care. Lambin described “rapid learning” as the use of data routinely generated through patient care and clinical research to feed an ever-growing database. Thanks to this database, Lambin hopes to be able to develop mathematical models – following the example of weather models – capable of “predicting the future”. Indeed, as Klaus Maier-Hein showed yesterday, simulation models really are a promising way to greatly improve cancer treatment and research. But to achieve that, computing scientists need huge amounts of data – data they are eager to collect all over the world through the Euregional Computer Assisted Theragnostics project (EuroCAT).

To conclude the morning session, Michael Campbell, from CERN, presented the Medipix and Timepix chips, which, although initially developed for CERN’s Large Hadron Collider experiments, quickly showed great potential for medical imaging.

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Michael Campbell during his Medipix talk. (Picture: Salvatore Fiore)

Campbell presented to the audience the very recent Medipix3, which permits spectroscopic X-ray imaging at high spatial resolution and relatively high fluxes by using inter-pixel hit-by-hit processing. The Timepix3 chip, on the other hand, takes the opposite approach, detecting each hit with a time precision of 1.6 ns and sending all data off chip for analysis, which is used for beam and dose monitoring during hadron therapy.

Noon sounded the end of Campbell’s talk, as all the participants joined the CICG main hall for a well-deserved lunch. We’ll all be back in 1 hour – stay tuned!

Anaïs Schaeffer


In the afternoon…

- Room 2 -

The first topic addressed in the afternoon session dedicated to novel approaches in imaging, which was chaired by Philippe Lambin, was cancerous cell hypoxia monitoring. As Brad Wouters, from the Princess Margaret Cancer Centre in Toronto, explained in his talk, many human tumors develop fast and end up outgrowing their blood supply, so that some regions of the tumor are left with an oxygen concentration significantly lower than in healthy tissue. Even though it might seem to be a positive effect, hypoxia actually promotes metastasis and resistance to most forms of therapy. As a consequence, being able to monitor the distribution and variation of tumor hypoxia is of paramount importance for the assessment of the treatment efficacy and its control. Wouters’ team has developed a series of small molecule probes with identical chemical structures, but containing different isotopes of tellurium that can be independently quantified. They allow measuring dynamic changes in tumor hypoxia at cellular level, both in vitro and in vivo model systems.

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Brad Wouters during his talk. (Picture: Salvatore Fiore)

The following speaker, Ester Troost from the Institute of Radiooncology and the University Hospital of Dresden, extended the discussion about functional imaging focusing on the necessity to move from pre-clinical to clinical setting and from animal to human application. The first step - as she said - is about ‘imaging the enemy’, which means getting a precise picture of the tumor as well as the hypoxic regions in it; this can be accomplished with a number of state-of-the-art imaging technologies. Then focus goes to the translational chain between laboratory and clinical setting: research pursued on animals in laboratory environment is actually gradually moving its steps on the clinical field, but according to Troots functional imaging has to be inserted in routine clinical practice.

The session was closed by Wouter van Elmpt, from the University Medical Centre of Maastricht, who talked about the future perspectives for dual energy computed tomography (DECT) scan for radiotherapy. Based on the use of X-ray of two different energies, it can selectively increase or decrease the effects of some chemical substances in the body, making some abnormalities clearer on the images taken. As a consequence, DECT may improve tumor detection and characterization, thus increasing the accuracy of the radiotherapy dose calculation.

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Ester Troost talking about functional imaging. (Picture: Salvatore Fiore)

The morning schedule moved on to a panel discussion about another fascinating topic: therapeutic targets. It is about different mechanisms or molecules necessary for survival and proliferation of cancer, which can be addressed as potential treatment targets. After the introduction by chairman Karin Haustermans, the floor was taken by Zvi Fuks, from the Memorial Sloan Kettering Cancer Centre of New York, who presented a dual target model for single dose radiotherapy (SDRT). The main mechanism involved in tumor cell killing by ionizing radiation is radiation-induced DNA double strand breaks (DSBs). Fuks reported on high (>10Gy) SDRT able to induce not only DSBs damage, but also microcirculatory ischemia/reperfusion injury, which compromises the DSB repair, resulting in increased effectiveness of the treatment.

New targets for cancer therapy can also be identified by studying in depth the processes involved in gene activation and transcription under cell hypoxia conditions, as explained by Amato Giaccia, from Stanford. Under low oxygen, mammalian cells show an adaptive response that leads to the induction of a number of genes with well-defined roles in oxygen supply and energy maintenance. Recent in vitro studies (employing transgenic mice) are giving important insights about these mechanisms, while allowing hypoxia-inducible genes cataloguing.

Finally, Michael Horsman, from Aarhus University Hospital, discussed new developments of research on agents able to disrupt the vasculature formed by the tumor in order to blood supply itself.

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Amato Giaccia during his talk. (Picture: Salvatore Fiore)

After the coffee break, an overview of immunology-based attack strategies was given in a short session chaired by Marcel Verheij. Kevin Harrington, from the Institute of Cancer Research (GB), presented his research on oncolytic viruses, i.e. viruses that preferentially infect and kill cancer cells. Preclinical studies showed that the combination of the T-VEC virus with immunotherapy increased tumor regression in mice, compared to single agents use. First trials of T-VEC virus exploitation on humans are ongoing and their efficacy in combination with other therapies is under evaluation.

Another point of view in this complex field of research was given by Eric Deutsch, from the Paris Sud University, who reported on promising results of new studies on the combination of local irradiation (radiotherapy) and vaccination for the treatment of head and neck squamous cell carcinoma, associated to human papillomavirus.

Last on the stage, Ludwig Dubois, of the University Medical Centre of Maastricht, presented interesting data on radiotherapy combined with immunotherapy oriented at stimulating the immune system to assist in eliminating cancer cells, within and outside the radiation field. In particular, tests based on the use of immunocytokine L19-IL2 showed long-lasting response.

The session closed but not the discussion about these diverse and intriguing topics. Anyway, it was time to get dressed up and go for the Gala dinner.

Virginia Greco

 

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Blogger Virginia Greco at work... (Picture: Salvatore Fiore)

 

- Room 3 -

At exactly 1 p.m. (as Jürgen Debus, co-chair of this session on particle therapy, observed: “Swiss precision!”), Thomas DeLaney took the floor to present the case of the Massachusetts General Hospital, in Boston. With a cyclotron of 230 MeV, 3 treatment rooms and an experimental room with horizontal beam, this centre treated 737 patients in 2015 alone, and more than 8350 over its 15 years of operation. Right after DeLaney, Johanna Salinger brought us back to this side of the Atlantic, in Austria, where MedAustron, the third centre for ion beam therapy and research in Europe, is about to treat its first patient with a horizontal proton beam. In a few years, MedAustron is expected to start treating patients also with carbon ions. After the United-States and Europe, ICTR-PHE had us land in Asia in less than 1 hour… as Zhen Zhang presented the very first particle therapy centre in China: the Fudan University Shanghai Cancer Centre.

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Zhen Zhang presents the first particle therapy centre in China. (Picture: Salvatore Fiore)

This centre, equipped with 220 beds, has been able, since May 2015, to treat patients with both proton and carbon ion beams. Zhang indicated that 2 other particle therapy centres are currently under construction in China, and that this number is expected to significantly increase over the coming years.

The afternoon continued with a panel discussion on the optimisation of treatment planning and delivery. For almost 2 hours, specialists from Switzerland, the United States and The Netherlands interacted with the audience and the chairs, Søren Bentzen and Hans Langendijk, on this key aspect of radio- and hadron-therapy. For example, some tumours can – and do – show anatomical changes along the whole treatment process, making it difficult to establish a rigid treatment planning – hence the need for a more dynamic planning and delivery process.

After the coffee break, the last topic of the afternoon really engaged the audience! Of concern to every oncologist (and patient!), the protection of normal tissues during radio- and hadron- therapy is a priority. What are the best strategies to reduce toxicity? Jean Bourhis, from the Swiss Cancer Centre in Lausanne, raised great interest (and many questions!) with his very recent results on motion management.

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Jean Bourhis answering the many questions of the audience. (Picture: Salvatore Fiore)

The movements patients do during therapy, when breathing for example, are a major issue as they hinder the localisation of the tumour. Bourhis presented 2 ways of getting around this problem: apnea-like suppression of respiratory motion, thanks to the use of percussion assisted ventilation, and single dose radiotherapy. With its extremely rapid single dose radiotherapy setup, called “FLASH”, Bourhis’ team is able to deliver 50 Gy in 400 ms… overtaking the problem of motion management.

On the same subject, Carlo Greco, from the Champalimaud Centre for the Unknown of Lisbon, showed that a 24 Gy single dose irradiation is much better than a fractionated one (3 x 9 Gy), while also being faster and more cost-effective. Read about Zvi Fuks’ work in Virginia Greco’s blog (see above) for more information on single dose radiotherapy.

After Carlo Greco’s presentation, questions and discussions went on in the room and the hall… and probably will continue at the well-deserved Gala dinner! 

Anaïs Schaeffer

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