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Kamada T.,Japan National Institute of Radiological Sciences | Tsujii H.,Japan National Institute of Radiological Sciences | Blakely E.A.,Lawrence Berkeley National Laboratory | Debus J.,University of Heidelberg | And 9 more authors.
The Lancet Oncology | Year: 2015

Charged particle therapy is generally regarded as cutting-edge technology in oncology. Many proton therapy centres are active in the USA, Europe, and Asia, but only a few centres use heavy ions, even though these ions are much more effective than x-rays owing to the special radiobiological properties of densely ionising radiation. The National Institute of Radiological Sciences (NIRS) Chiba, Japan, has been treating cancer with high-energy carbon ions since 1994. So far, more than 8000 patients have had this treatment at NIRS, and the centre thus has by far the greatest experience in carbon ion treatment worldwide. A panel of radiation oncologists, radiobiologists, and medical physicists from the USA and Europe recently completed peer review of the carbon ion therapy at NIRS. The review panel had access to the latest developments in treatment planning and beam delivery and to all updated clinical data produced at NIRS. A detailed comparison with the most advanced results obtained with x-rays or protons in Europe and the USA was then possible. In addition to those tumours for which carbon ions are known to produce excellent results, such as bone and soft-tissue sarcoma of the skull base, head and neck, and pelvis, promising data were obtained for other tumours, such as locally recurrent rectal cancer and pancreatic cancer. The most serious impediment to the worldwide spread of heavy ion therapy centres is the high initial capital cost. The 20 years of clinical experience at NIRS can help guide strategic decisions on the design and construction of new heavy ion therapy centres. © 2015 Elsevier Ltd.


Pella A.,Polytechnic of Milan | Riboldi M.,Polytechnic of Milan | Riboldi M.,CNAO Foundation | Tagaste B.,CNAO Foundation | And 11 more authors.
Technology in Cancer Research and Treatment | Year: 2014

In an increasing number of clinical indications, radiotherapy with accelerated particles shows relevant advantages when compared with high energy X-ray irradiation. However, due to the finite range of ions, particle therapy can be severely compromised by setup errors and geometric uncertainties. The purpose of this work is to describe the commissioning and the design of the quality assurance procedures for patient positioning and setup verification systems at the Italian National Center for Oncological Hadrontherapy (CNAO). The accuracy of systems installed in CNAO and devoted to patient positioning and setup verification have been assessed using a laser tracking device. The accuracy in calibration and image based setup verification relying on in room X-ray imaging system was also quantified. Quality assurance tests to check the integration among all patient setup systems were designed, and records of daily QA tests since the start of clinical operation (2011) are presented. The overall accuracy of the patient positioning system and the patient verification system motion was proved to be below 0.5 mm under all the examined conditions, with median values below the 0.3 mm threshold. Image based registration in phantom studies exhibited sub-millimetric accuracy in setup verification at both cranial and extra-cranial sites. The calibration residuals of the OTS were found consistent with the expectations, with peak values below 0.3 mm. Quality assurance tests, daily performed before clinical operation, confirm adequate integration and sub-millimetric setup accuracy. Robotic patient positioning was successfully integrated with optical tracking and stereoscopic X-ray verification for patient setup in particle therapy. Sub-millimetric setup accuracy was achieved and consistently verified in daily clinical operation. © Adenine Press (2014).


Riboldi M.,Polytechnic of Milan | Riboldi M.,Bioengineering Unit | Orecchia R.,CNAO Foundation | Orecchia R.,Oncology and Radiotherapy Institute | And 3 more authors.
The Lancet Oncology | Year: 2012

A key challenge in radiation oncology is accurate delivery of the prescribed dose to tumours that move because of respiration. Tumour tracking involves real-time target localisation and correction of radiation beam geometry to compensate for motion. Uncertainties in tumour localisation are important in particle therapy (proton therapy, carbon-ion therapy) because charged particle beams are highly sensitive to geometrical and associated density and radiological variations in path length, which will affect the treatment plan. Target localisation and motion compensation methods applied in x-ray photon radiotherapy require careful performance assessment for clinical applications in particle therapy. In this Review, we summarise the efforts required for an application of real-time tumour tracking in particle therapy, by comparing and assessing competing strategies for time-resolved target localisation and related clinical outcomes in x-ray radiation oncology. © 2012 Elsevier Ltd.


Cerutti F.,CERN | Ferrari A.,CERN | Mairani A.,CNAO Foundation | Sala P.R.,National Institute of Nuclear Physics, Italy
CERN-Proceedings | Year: 2013

FLUKA is a general purpose tool for calculations of particle transport and interactions with matter. It handles all hadrons, ions, and electromagnetic particles. The FLUKA applications range from LHC or cosmic energies down to hadron-therapy and microdosimetry. It is the standard tool at CERN for beam-machine interactions and radioprotection. All FLUKA models and algorithms are object of a long and constant development that benefits to a wide range of applications. The present paper will focus on selected new developments in the nuclear interaction models, namely: hadronic interactions in the few GeV energy range and their effect on neutrino induced reactions; interactions of α particles below 150 MeV/A; improvements in the latest stages of nuclear reactions.


PubMed | University of Pavia, University of Bologna, ENEA, Italy CNAO Foundation and 2 more.
Type: Comparative Study | Journal: Radiation protection dosimetry | Year: 2015

A comparative study has been performed on the effects of high-dose-rate (DR) X-ray beams produced by a plasma focus device (PFMA-3), to exploit its potential medical applications (e.g. radiotherapy), and low-DR X-ray beams produced by a conventional source (XRT). Experiments have been performed at 0.5 and 2 Gy doses on a human glioblastoma cell line (T98G). Cell proliferation rate and potassium outward currents (IK) have been investigated by time lapse imaging and patch clamp recordings. The results showed that PFMA-3 irradiation has a greater capability to reduce the proliferation rate activity with respect to XRT, while it does not affect IK of T98G cells at any of the dose levels tested. XRT irradiation significantly reduces the mean IK amplitude of T98G cells only at 0.5 Gy. This work confirms that the DR, and therefore the source of radiation, is crucial for the planning and optimisation of radiotherapy applications.


Kase Y.,Japan National Institute of Radiological Sciences | Kase Y.,Proton Therapy | Himukai T.,Japan National Institute of Radiological Sciences | Nagano A.,Japan National Institute of Radiological Sciences | And 8 more authors.
Journal of Radiation Research | Year: 2011

Cerebral radionecrosis is a significant side effect in radiotherapy for brain cancer. The purpose of this study is to calculate the relative biological effectiveness (RBE) of carbon-ion beams on brain cells and to show RBE-weighted dose distributions for cerebral radionecrosis speculation in a carbon-ion treatment planning system. The RBE value of the radionecrosis for the carbon-ion beam is calculated by the modified microdosimetric kinetic model on the assumption of a typical clinical α/β ratio of 2 Gy for cerebral radionecrosis in X-rays. This calculation method for the RBE-weighted dose is built into the treatment planning system for the carbon-ion radiotherapy. The RBE-weighted dose distributions are calculated on computed tomography (CT) images of four patients who had been treated by carbon-ion radiotherapy for astrocytoma (WHO grade 2) and who suffered from necrosis around the target areas. The necrotic areas were detected by brain scans via magnetic resonance imaging (MRI) after the treatment irradiation. The detected necrotic areas are easily found near high RBE-weighted dose regions. The visual comparison between the RBE-weighted dose distribution and the necrosis region indicates that the RBE-weighted dose distribution will be helpful information for the prediction of radionecrosis areas after carbon-ion radiotherapy.


PubMed | Japan National Institute of Radiological Sciences, CNAO Foundation and University of Milan
Type: Journal Article | Journal: Radiation protection dosimetry | Year: 2015

In this article, the in vivo study performed to evaluate the uniformity of biological doses within an hypothetical target volume and calculate the values of relative biological effectiveness (RBE) at different depths in the spread-out Bragg peak (SOBP) of the new CNAO (National Centre for Oncological Hadrontherapy) carbon beams is presented, in the framework of a typical radiobiological beam calibration procedure. The RBE values (relative to (60)Co rays) of the CNAO active scanning carbon ion beams were determined using jejunal crypt regeneration in mice as biological system at the entrance, centre and distal end of a 6-cm SOBP. The RBE values calculated from the iso-effective doses to reduce crypt survival per circumference to 10, ranged from 1.52 at the middle of the SOBP to 1.75 at the distal position and are in agreement with those previously reported from other carbon ion facilities. In conclusion, this first set of in vivo experiments shows that the CNAO carbon beam is radiobiologically comparable with the NIRS (National Institute of Radiological Sciences, Chiba, Japan) and GSI (Helmholtzzentrum fr Schwerionenforschung, Darmstadt, Germany) ones.


Rossi S.,CNAO Foundation
Physica Medica | Year: 2015

The National Centre for Oncological Hadrontherapy (CNAO, sited in Pavia, Italy) completed at the end of 2013 the clinical trial phase achieving the CE label from the notified body of the Italian Health Ministry and obtained the authorisation to treat patients within the national health system. Nowadays more than 400 patients completed the treatments, two thirds of them with carbon ions, and recently started the treatment of pathologies located within moving organs. For the first time in the world carbon ions delivered with active scanning, coupled with breathing synchronisation and rescanning modalities have been applied to treat patients affected by tumours of the liver and by pancreatic cancers.The path to reach the final CE label required a wide-ranging experimental activity that went through dosimetry measurements of the hadron beams, in-vitro and in-vivo radiobiology essays and treatments of 150 patients, all enrolled in one of the 23 clinical trials approved by the Ethical Committee of CNAO and then authorized by the Italian Ministry of Health. The results of the trials were very positive in terms of safety and reliability of the procedures. The follow-up period is still short, but preliminary good results are observed in particular in terms of limited toxicity, that on the whole is less than expected.The paper gives a status report on the experimental phase that completed the CE certification process and then outlines the ongoing activities with also indications on the future trends and the most interesting R&D programmes pursued at CNAO. © 2015 Associazione Italiana di Fisica Medica.


Rossi S.,CNAO Foundation
Nuclear Physics News | Year: 2013

The CNAO (Italian acronym that stands for National Centre for Oncological Hadrontherapy) began its clinical activity in September 2011 with the launch of the experimental treatments with beams of protons. In November 2012 the first patient was treated with carbon ions. On both occasions it was an absolute novelty in the panorama of Italian healthcare. © 2013 Copyright Taylor and Francis Group, LLC.


PubMed | CNAO Foundation
Type: Journal Article | Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) | Year: 2015

The National Centre for Oncological Hadrontherapy (CNAO, sited in Pavia, Italy) completed at the end of 2013 the clinical trial phase achieving the CE label from the notified body of the Italian Health Ministry and obtained the authorisation to treat patients within the national health system. Nowadays more than 400 patients completed the treatments, two thirds of them with carbon ions, and recently started the treatment of pathologies located within moving organs. For the first time in the world carbon ions delivered with active scanning, coupled with breathing synchronisation and rescanning modalities have been applied to treat patients affected by tumours of the liver and by pancreatic cancers. The path to reach the final CE label required a wide-ranging experimental activity that went through dosimetry measurements of the hadron beams, in-vitro and in-vivo radiobiology essays and treatments of 150 patients, all enrolled in one of the 23 clinical trials approved by the Ethical Committee of CNAO and then authorized by the Italian Ministry of Health. The results of the trials were very positive in terms of safety and reliability of the procedures. The follow-up period is still short, but preliminary good results are observed in particular in terms of limited toxicity, that on the whole is less than expected. The paper gives a status report on the experimental phase that completed the CE certification process and then outlines the ongoing activities with also indications on the future trends and the most interesting R&D programmes pursued at CNAO.

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