Manjit Dosanjh. CERN, European Organization for Nuclear Research,CH-1211 Geneva 23, Switzerland. ENLIGHT, European Network for Light ion Therapy, ...
Development of Hadron Therapy for Cancer Treatment in Europe Manjit Dosanjh
Citation: AIP Conference Proceedings 1032, 12 (2008); doi: 10.1063/1.2979248 View online: https://doi.org/10.1063/1.2979248 View Table of Contents: http://aip.scitation.org/toc/apc/1032/1 Published by the American Institute of Physics
Development of Hadron Therapy for Cancer Treatment in Europe Manjit Dosanjh CERN, European Organization for Nuclear Research,CH-1211 Geneva 23, Switzerland ENLIGHT, European Network for Light ion Therapy, www.cern.ch/enlight Abstract. The European Network for LIGht ion Hadron Therapy aims at a coordinated effort towards ion beam research in Europe. ENLIGHT network is formed by the European Hadron Therapy Community which consists of more than 150 researchers and specialists, belonging to more than fifty European Universities and research Institutes from sixteen European countries. ENLIGHT has demonstrated the advantages of regular and organised exchanges of data, information, best practices as well as information on treatment procedures, protocols and strategies. A major success of ENLIGHT has been the creation of a multidisciplinary platform, uniting traditionally separate communities so that clinicians, physicists, biologists and engineers with experience and interest in particle therapy work together. Keywords: Radiation biology, hadron therapy, cancer treatment, ENLIGHT.
HISTORY AND CURRENT STATUS OF HADRON THERAPY Cancer is a major societal health problem and currently, approximately 11 million people worldwide are diagnosed with cancer, and almost 7 million people die of the disease each year. Additionally, more than 25 million people are surviving for years after a cancer diagnosis. By 2020, more than 16 million new cancer cases and 10 million cancer deaths are expected annually. Seventy percent of these deaths will likely occur in developing countries that are unprepared to address their growing cancer burden. In Europe, each year 1.8 million Europeans develop malignant tumours and it is predicted to become the leading cause of death in the next decade. About 50% of the patients are cured and radiotherapy (RT) accounts for 40% of this figure, either alone (24%) or in combination therapy. RT plays also an important role in symptom control and pain relief for incurable patients. RT is by far the most cost-effective modality for curative cancer treatment while conserving tissue function. With increasing cancer incidence and the impact of an ageing population, the role of radiotherapy will further increase over the next decades. Ion therapy offers new hope especially to those patients whose tumours cannot be treated by surgery or with conventional radiotherapies.
CP1032, Medical Physics - Tenth Symposium on Medical Physics, edited by G. Herrera Corral and L. M. Montaño Zetina © 2008 American Institute of Physics 978-0-7354-0556-1/08/$23.00
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The main aim of radiation therapy is to deliver a maximally effective dose of radiation to a designated tumour site while sparing the surrounding healthy tissues as much as possible. Conventional X-ray radiation therapy is characterised by almost exponential attenuation and absorption, and consequently delivers the maximum energy near the beam entrance, but continues to deposit significant energy at distances beyond the cancer target. To compensate for the disadvantageous depth-dose characteristics of X-rays and to better conform the radiation dose distribution to the shape of many cancers, the radiation oncologists use complex Conformal or Intensity Modulated Radiation Therapy techniques (IMRT). These involve the use of computer-aided treatment plan optimization tools achieving a better dose conformity and minimizing the total energy deposition to the normal tissues. For charged particles, there is a large reduction of at least 50% (and frequently larger) in the total energy, or integral dose, deposited in the body with a corresponding reduction in normal tissue damage. Visionary physicist and founder of Fermi lab, Robert Wilson proposed the use of hadrons for cancer treatment in 1946. This idea was first applied at the Lawrence Berkeley Laboratory (LBL) where 30 patients were treated with protons between 1954–1957. RT with hadrons (protons and light ions, in particular carbon ions) offers several advantages. The heavier charged hadrons penetrate the patient with minimal lateral diffusion and deposit their maximum dose at the end of their range, effectively sparing all deeper tissues. The cancer dose profile can be very precisely shaped using narrow focused and scanned pencil beams of variable penetration depth. Protons have similar biological effect as X-rays but different depth dose profile, with the highest dose at the end of their range. Thus, in some cases, lower tissue damage can be obtained than using X-rays. Protons have a biological effect of around 10% higher than X rays, but deposit less energy in healthy tissues. Thus with protons, a higher tumour control probability can be obtained if dose is increased while allowing reduced complications in a larger volume of normal surrounding tissue. Proton therapy is booming, with about 50,000 patients treated worldwide. Several dedicated hospital-based centres with significant capacity for treating patients are now replacing the first generation R&D facilities hosted by the physics research laboratories. In Europe protontherapy centres for deep-seated tumours exists in Orsay (France), Munich (Germany), Uppsala (Sweden), Villigen (Switzerland). Moreover various facilities exists which produce lower energy proton beams to treat eye melanomas. Today, five companies offer turn-key centres and about ten new centres are under construction around the world. However, less than 1% of the patients have been irradiated with the more technologically advanced ‘active’ scanning techniques, which are an exclusive European contribution developed recently at PSI (Villigen) for protons and at GSI (Darmstadt) for carbon ions. Carbon ions deposit about 24 times more energy in a cell than protons having the same range. In the last centimetres of the range the Linear Energy Transfer (LET) is much larger than the one of X-rays and protons (low-LET radiations). The resulting DNA
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damages include more complex double strand breaks and lethal chromosomal aberrations, which cannot be repaired by the normal cellular mechanisms. From the entrance point to about 5 cm before the end of the range in tissue, carbon ions deposit lower energy densities behaving as low-LET radiations and the DNA damage is more repairable. The effects produced at the end of the range are qualitatively different from those produced by the other classes of radiations and open the way to implement a strategy to treat radio-resistant, often due to hypoxia of the tumour cells. For these reasons carbon ions with their higher relative biological effectiveness (RBE) at the end of their range, they are around three times more effective at killing cells, consequently can control tumours that are normally resistant to X-rays and even possibly protons. Europe is playing a key role in the development of ion therapy. In 1997 for the first time treatments with actively scanned carbon ions were performed at the GSI centre (Gesellschaft für Schwerionenforschung) in Germany. Light ion therapy ‘dual’ centres (for both carbon ions and protons) are presently under construction in Heidelberg (Germany) and Pavia (Italy). Additional dual hadron therapy centres have been approved in Austria, France, and Germany and a number of other European countries are interested in establishing more proton and ion therapy centres. Close cooperation between scientists and the clinical community is needed to make advanced technology clinically effective and reliable. The technological objective is to pool available expertise to avoid duplication, speed up development and meet the stringent criteria imposed by clinical applications. By ordering jointly components to industry, costs could be cut and a better quality control during construction, installation and running achieved. ENLIGHT, which had its inaugural meeting at CERN in February 2002, was established to coordinate European efforts in using light-ion beams for radiation therapy. Funded by the European Commission for three years (2002-2005), the network was formed from a collaboration of European centres, institutions, and scientists, all involved in research and in the promotion and realization of ion therapy facilities in Europe. The ENLIGHT network has been instrumental in bringing together different European centres to promote hadron therapy, in particular with carbon ions, to help establish international discussions comparing the respective advantages of intensity modulated radiation treatment (IMRT), proton and carbon therapies and to address the ancillary equipment and methods necessary for such therapies. These efforts have included a study launched to compare the clinical data for proton therapy and carbon-ion therapy for certain types of tumour. Recently, an extended proto-collaboration called ENLIGHT++ was initiated with participation of the original ENLIGHT members and many new institutions all interested in the development of hadron cancer therapy. The aim of ENLIGHT++ network is twofold: to maintain and enlarge the European network of Institution and specialist which work in the field of Light Ion Therapy and to sponsor the research in fields of common interests for the development of the
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cutting edge and technically advanced clinical facilities. For this second aspect several research activities have been selected. The development of hadron therapy has been relatively slow, because it uses large apparatus by medical standards – a circular accelerator to provide the beams, and magnetic beam lines to deliver them to patients via large ‘gantries’. Cyclotrons or synchrotrons are used to produce protons with the energies needed for reaching deepseated tumours, while 20 metre diameter synchrotrons are used for carbon-ion beams. These complex high-tech systems could not be designed and run effectively and continuously - as required in a hospital environment - were it not for the experience developed for understanding the subatomic world through research in nuclear and particle physics. By the end of 2007, around 54 000 patients had been treated with proton beams in a dozen subatomic physics laboratories and in about five hospital-based proton therapy centres. Another ten centres are running-in or under construction in the world. By the same time around 4500 patients had been treated with carbon ions at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in Japan and about 400 at the ‘pilot project’ at the nuclear physics laboratory GSI in Darmstadt. In the past five years Europe – with initiatives at GSI and CERN - has made important steps in joining Japan in the development and construction of hospital-based dual centres for protons and carbon ions. Based on the successes of the pilot project, the Heidelberg Ion Therapy (HIT) Centre designed by GSI was approved in 2001 and first treatment will take place this year (2008). The construction project of the Italian National centre CNAO started in 2002 and will be finished by the end of this year (2008). Further centres are under construction or planned Marburg in Germany, Wiener Neustadt in Austria and ETOILE in France. Industry has shown considerable interest in the upcoming market of hadron therapy. Five companies (IBA, Siemens, Hitachi, Optivus and Varian-ACCEL) are now selling proton therapy units, and two firms (Siemens and Hitachi) have designed facilities for combined proton-carbon beams. beams. The strong interest of industrial companies in ion therapy indicates the large potential of this strategy for fighting cancer, which is rooted in the instruments developed for fundamental research in subatomic physics.
CONCLUSIONS At present, after many years in which hadron therapy was available only in a few centres across the world, there is now a strong interest in this treatment modality among the oncology community. In future, several more centres are expected to be built in Europe. Together they will provide the basis for a general extension of hadron therapy to more tumour sites, with the potential of benefiting an even wider number of patients.
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In order to improve the effectiveness of hadron therapy, optimize return-on-investment and maximize synergy of the installations, the existing (and future) centres should be opened in order to create a common and non-competitive platform. Jointly they can improve and coordinate the research for more advanced tools and support a collaborative network of hadron therapy centres. By working closely together and with other European cancer centres, they will be in the best position to identify a common medical and scientific-technological strategy and integrate it into the oncological community. The main objective our collaboration ENLIGHT is and has been to form a consensus from representatives of different disciplines and national programmes in a way that most benefits the patient. It was agreed that this goal can be met by reinforcing the existing pan-European network and focusing on two complementary aspects: the research in areas needed for effective hadron therapy, and the networking needed for establishing and implementing common standards and protocols for treating patients. A similar approach could be used by the Mexican scientific community to open dialogue with the research and clinical community with appropriate health officials and funding agencies as well as companies, which could be interested in such a multidisciplinary effort. The ENLIGHT community will be happy to share its experiences and the lessons learnt in trying to form such a multidisciplinary platform with the Mexican researchers if desired.
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