In the morning...
- Room 2 -
The fourth day of conference started very early (at 8:15 a.m.), and even though yesterday night the participants enjoyed food and wine at the social dinner until late, the room was full. That was due to the very interesting program of the morning, which kicked off with a talk from such a renowned scientist as Søren Bentzen, who discussed about the necessity to combine precise medicine to multimodality treatment (surgery, radiotherapy, chemotherapy, etc.) in order to offer to the patient a tailored therapy.
Søren Bentzen during his talk. (Picture: Salvatore Fiore)
Later, an overview of the state of clinical trials for particle therapy in different countries was given in a high-participated session chaired by Vikram Bhadrasain and Roberto Orecchia. James Cox, from MD Anderson Cancer Centre in Texas, presented the current situation in the U.S., where 17 particle facilities operate delivering protons, while no one perform carbon ions treatment yet. Clinical trials, which have to follow precise protocols, are necessary in order to find evidence that proton therapy is superior to treatments with photons in terms of tumor control, patient survival, and treatment toxicity. According to Cox, clinical trials for particle therapy can hardly be conducted in the U.S., due to a number of structural biases, such as: cost (influencing the age and the social status of the patients); subjectivity in scoring acute and sub/acute effects; patient acceptance; as well as expertise of the investigators. Moreover, most of the studies don’t take into account late effects (including second malignant neoplasm), which -on the contrary- are very important in order to assess treatment toxicity.
James Cox (on the left) and Jürgen Debus (on the right) presenting the situation of clinical trials for particle therapy in the U.S. and in Germany. (Pictures: Salvatore Fiore)
The situation looks better in Germany, as confirmed by the following speaker, Jürgen Debus, from the Heidelberg University Hospital (HIT). That is because in Germany, as in UK, there is the obligation to include patients in clinical trials when treated in proton therapy centers. Both HIT and Malburg’s center can deliver protons and carbon ions: only at HIT in 2015 were treated more than 700 patients. Clinical trials with protons are ongoing also in the University Hospital of Dresden and the one of Essen.
Both proton and carbon-ion therapies are largely applied in Japan, as accounted by Hirohiko Tsujii, from the National Institute of Radiological Sciences in Chiba, thanks to the total 13 charged particle therapy facilities spread over the country, 9 of which deliver proton beams and 4 carbon ion. Several other facilities are also under construction. More than 9,000 patients have been treated so far adopting 70 protocols: these trials have been able to demonstrate the benefits of carbon ion radiotherapy, over other modalities, in locally advanced tumors and non-squamous cell types of cancer.
Hirohito Tsujii reporting on particle therapy in Japan. (Picture: Salvatore Fiore)
The second part of the morning was dedicated to a group of presentations about achievements accomplished by the European Organization for Research and Treatment of Cancer (EORTC), whose aims are to develop, conduct, coordinate, and stimulate translational and clinical research on cancer in Europe. Damien Weber, from PSI in Switzerland, and André Branquinho, from EORTC headquarter in Brussels, described the radiotherapy quality assurance (RTQA) platform, which aims at defining the range of possible variations to clinical trial protocols that are acceptable, without compromising the study results.
At this point, the floor was taken in turns by three women. Sofia Rivera, from Gustave Roussy Cancer Campus Grand Paris, reported on various projects oriented at developing radiotherapy-targeted agents combination treatments, which apparently are yet not seen as a priority by industry. The most difficult part, explained Rivera, is getting funding for pre-clinical assessment (a fundamental phase in trials protocol), in particular when some clinical data is already available.
Sofia Rivera (on the left) and Monika Hegi (on the right) during their talks. (Pictures: Salvatore Fiore)
A new screening of patients for efficient clinical trials (SPECTA) program has been launched by EORTC for research on glioblastoma (GBM), as explained by Monika Hegi, from the University Hospital of Lausanne. This malignant brain tumor is known for its resistance to therapies, likely due to various genetic and epigenetic alterations that enhance the ability of growing cancerous tissues to rapidly mutate and adapt to environmental variations. This kind of tumor is normally treated with radiotherapy in combination with temozolomide, an adjuvant oral drug. Clinical trials are exploring new possible combinations of therapies. In this scenario, the capacity to identify sub-categories of patients on the base of the molecular profiles of their tumor, and to choose the most adequate drug for them, is key to increasing the chances of success.
Finally, Conny Vrieling, from the Clinique des Grangettes in Geneva, tackled the sensitive issue of long-term side effects of cancer therapies, which span treatment-induced diseases, second malignancies, fatigue, infertility, chronic pain, and even psycho-social problems.
- Room 3 -
After the first talk in Room 2, people quickly joined Room 3 for the beginning of the Genomics session. We started here with a presentation by Dirk De Ruysscher, from the University Medical Centre of Maastricht, about genetic predictors of radiotherapy response. De Ruysscher projected very interesting graphs showing patients’ individual radiosensitivity curves, which indicate that most patients are in one of these 3 categories: high radiosensitivity, medium radiosensitivity and low radiosensitivity. However, some very rare patients do show a severe and even extreme radiosensitivity. De Ruysscher’s team studied 9 of these patients and saw that all isn’t “black and white”: the radiosensitivity depends on which organ is being treated. It appears that there definitely is a genetic cause for some of the observed individual differences in radiosensitivity.
We then had the opportunity to go a bit further into the biology of the irradiation process, thanks to Frederic Zenhausern, from the University of Arizona, who presented a new tool to analyse molecular biomarkers. Biomarkers are essential to understand the mechanisms of radiation exposure in human tissue, in particular the biological mechanisms of tissue damage and recovery. Zenhausern demonstrated how novel technologies using body fluids - blood and derivatives substances (serum, plasma…), as well as saliva, urine, etc - have revealed molecular information that will open the doors for new clinical understanding in oncology. And in the future, the convergence of imaging features analysis and molecular biomarkers will certainly provide powerful tools for guiding radiotherapies.
After Zenhausern’s talk, radiotherapists and the biologists continued their discussions in the room before grabbing a coffee just on time for the start of the second session: Detectors and Imaging, chaired by Paul Lecoq and Katia Parodi, so…. Welcome now in the techy world! (For more information about "Detectors and Imaging", read Virginia Greco's blog published on Tuesday morning).
Valeria Rosso, from the University of Pisa and INFN, and Saad Aldawood, from the Ludwig Maximilians University of Munich and the King Saud University of Riyadh, presented new ways to monitor particle beams: the DoPET system and the Compton camera, respectively. During particle irradiation, various ß+-emitting isotopes are generated in the patient and this activity distribution can be related to the delivered dose.
Valeria Rosso describes the DoPET system. (Picture: Salvatore Fiore)
With a compact PET system, called DoPET and based on two planar detecting heads, Rosso’s team managed to reconstruct the distal fall activity profile with a sensibility of 1 mm, operating in-treatment. The Compton camera, on the other hand, is an online imaging system capable of monitoring the particle beam range by detecting prompt γ rays generated by nuclear reactions occurring between the particle beam and the biological tissue (Thomas Bortfeld, from the Massachusetts General Hospital and Harvard Medical School presented similar studies on Tuesday morning). It consists of two main components: a scatterer (tracker) and a monolithic LaBr3 scintillation detector acting as an absorber detector.
The session ended a bit earlier so that the scientists could continue to exchange their views and share their specific experience, but still be first in line for lunch!
In the afternoon…
- Room 2 -
The afternoon session opened up with a talk by Brad Wouters, who accepted the E. van der Schueren Award bestowed to the Princess Margaret Cancer Centre of Toronto, and moved on to a discussion on Radio-Biological Effectiveness (RBE). Marco Durante, from GSI (Darmstadt, Germany), was asked to give a general overview of in-vitro research on RBE. Right after, Piero Fossati, from CNAO (Italy), and Tony Lomax, from PSI (Switzerland), completed the picture discussing some other aspects of RBE, such as the issue of the models adopted to define the dose on the base of the RBE of the used particles on the specific tissue.
Marco Durante talking about in-vitro RBE. (Picture: Salvatore Fiore)
After a long coffee break dedicated to the poster session, chairmen Jacques Balosso and Damien Weber called to the stage Roberto Orecchia, from CNAO, who reported on the state of particle therapy at the Italian Center for Oncologic Hadrontherapy. CNAO has entered its fifth year of clinical activity and has treated almost 700 patients up to November 2015. The center delivers treatments with both protons and carbon ions: patients treated with carbon ions are about three times those treated with protons An important goal reached in the last year was also the treatment of tumors located in moving organs, for which the vertical beam line was used along with gating and rescanning technologies, that allow an online control of the position of the target.
The talk of Hans Langendijk, from the Center for Image Sciences of Utrecht (the Netherlands) closed the fourth day of the conference. He presented the particle therapy program financed by the Dutch Ministry of Health. Four brand new treatment centers will be established, with a geographic distribution over the country that will allow optimal accessibility to all eligible patients.
Brad Wouters with the E. van der Schueren Award, bestowed to the Princess Margaret Cancer Centre of Toronto. (Picture: Salvatore Fiore)
- Room 3 -
This morning, Dirk De Ruysscher showed that there is a genetic cause in the variability of radiosensitivity among patients, but what if oncologists could get around this predisposition? What if they could modulate the tumour cell radiosensitivity? That’s the subject of this new session, chaired by Jacques Bernier and Jean Bourhis.
At the Netherlands Cancer Institute, Marcel Verheij and his team work on novel agents targeting cell membrane in order to improve the tumour cells radiosensitivity. The cell membrane acts as a physical barrier between the intracellular and extracellular space, but it also plays an important role in receptor-ligand interactions, signal transduction and drug uptake.
Marcel Verheij (left) during the coffee break. (Picture: Salvatore Fiore)
Targeting the cell membrane thus seems a good strategy to improve anti-cancer therapy. In his talk, Verheij presented a study showing that co-formulation and co-administration of liposome-encapsulated chemotherapy and synthetic short-chain sphingolipids (SCS) succeed to improve drug effectiveness by enhancing intracellular drug uptake.
During the coffee break, the participants had the opportunity to have a thorough look at the posters exposed in the hall of the conference centre (don't miss the presentation of the winning posters tomorrow at 12:45 a.m. in Room 4!). They went back at 16:15 p.m. for the last session of the day: emerging challenges in combating cancer, chaired by Vincent Grégoire.
Norman Coleman, senior scientific advisor to the International Cancer Expert Corps (ICEC) and member of the US National Cancer Institute, took the floor first. He gave a very interesting and engaged presentation on the history and mission of the non-governmental organization ICEC. Coleman highlighted that today, 30 African and Asian countries still don’t have access to interventions to prevent and treat cancer and its symptoms, and there is still a shortfall of 5000 radiotherapy machines in the developing world. The mission of the ICEC is to implement a global force to address this problem, through a mentoring network of cancer professionals who work with local and regional in-country groups to develop and sustain expertise for better cancer care.
As an echo to the global vision of Norman Coleman, Ritsuko Komaki, from the University of Texas, reminded that lung cancer is the leading cause of cancer-related death throughout the world. She particularly focused her presentation on former and current smoking patients and shared encouraging results showing that early detection involving the use of low-dose spiral computed tomography (CT) among those patients led to a 20% reduction in the rate of lung-cancer death.