- Email: [email protected]
201: The ULICE project
S98
ICTR-PHE – 2014
Material and Methods: The Compton telescope will consist of three detector layers and each layer will be made of a continuous LaBr3 crystal coupled to four Silicon Photomultiplier (SiPM) arrays. A two layer prototype of the telescope has already been built 2
up and tested. Each layer is composed of a 32x36 mm LaBr3 crystal coupled to four SiPM arrays. The first detector (placed closer to the radioactive source) is 5 mm thick, the second one is 10 mm thick. Each SiPM array, from Hamamatsu Photonics (S11064-050P(X1)), consists of 16 (4x4) Multi Pixel Photon Counter (MPPC) with elements of 3 mm x 3 mm size, each one composed of 3600 microcells of 50 µm x 50 µm size. The MPPC arrays are placed in a custom made hybrid board that provides mechanical support, the bias for the MPPC arrays and also hosts a VATA64HDR16 ASIC from Gamma Medicas-Ideas, employed to read-out the 64 detector channels. Each hybrid board is connected to a data acquisition system (DAQ) developed at IFIC and equipped with an FPGA that provides the configuration for the ASIC and the control of the acquisition process. A third detector layer 3
of the telescope, made of a 27.2x26.8x5 mm LaBr3 crystal coupled to four SiPM arrays, has been assembled and tested. Each SiPM array consists of 16 (4x4) MPPC from Hamamatsu (S11830-3344MF), with elements of 3 mm x 3 mm size. The energy resolution obtained in the preliminary tests with the third detector layer is 6.6% FWHM at 511 keV. Results: Coincidence tests have been carried out with the two layer telescope, placing the two detectors 41 mm apart and a
22
Na source 49 mm far from the first detector. Photons 22
emitted by a Na source that are Compton scattered in the first detector and interact also in the second, have been 22
collected. Images of a Na point-like source have been reconstructed employing a ML-EM algorithm, determining the correct functioning of the prototype. Conclusions: A two layer Compton Camera with continuous LaBr3 crystals coupled to SiPM arrays has been assembled and
tested. Coincidence tests have been successfully performed and allow the reconstruction of a 22Na point-like source. Inbeam tests have been performed at the CNA (National Accelerator Center) in Seville. A cyclotron providing an 18 MeV proton beam, was used to irradiate quartz and graphite targets. The in-beam coincidence data processing is ongoing. 200 Current Status of Carbon-Ion Radiotherapy at NIRS H. Tsujii National Institute of Radiological Sciences (NIRS), Chiba, Japan Introduction: In June 1994, the NIRS initiated carbon ion radiotherapy (C-ion RT) with HIMAC that was built as a part of the nation’s “Overall 10-year anti-cancer strategy in
Japan”. Since then, the HIMAC has served as a multipurpose facility that is jointly used for cancer therapy and fundamental studies. In 2010, a new treatment building with three rooms was built to use beam lines extending from the HIMAC. This was designed to administer adaptive charged particle therapy with pencil beam scanning, as well as to develop a compact rotating gantry [1]. Treatment with the scanning method started in 2011, and its indications have since been expanded to many types of tumors [2]. Materials/Methods: Initially, phase I/II trials were performed in order to confirm the safety and efficacy of C-ion RT, with the fraction number and treatment time being fixed for each tumor. In this way, the total dose was escalated in successive increments of 5 to 10%. Consistent efforts have been made to provide C-ion RT on an ethically and scientifically sound basis under a number of Committees. Results: As of August 2013, the total number of patients registered is more than 7,700. The experiences to date indicate that C-ion RT is advantageous for the following tumors: skull base tumors, head and neck cancer (adenocarcinoma, adenoid cystic carcinoma, malignant melanoma), NSCLC (early stage, locally advanced tumors), hepatocellular cancer, pancreatic cancer, prostate cancer, rectal cancer (postoperative pelvic recurrence), bone/soft tissue sarcoma of the pelvis, paraspinal region and head/neck, and uterine cervix adenocarcinoma. Tumors located in the vicinity of critical organs such as the eye, spinal cord and digestive tract with a relatively large size and/or irregular shape have also been effectively treated. However, tumors that infiltrate or originate in the digestive tract are difficult to control with C-ion RT. Regarding dose fractionations, a significant reduction in fractions has been obtained with acceptable toxicities in most cases. For example, stage I lung cancer and liver cancer can be treated with only one or two fractions, respectively. Even for prostate cancers, 12 to16 fractions have been sufficient. Currently, the number of irradiation sessions per patient averages 12 fractions spread over approximately three weeks. Conclusions: Clinical advantages have been demonstrated in the treatment of several types of tumors with C-ions, in particular, non-squamous cell type of tumors, and locally advanced, large tumors with acceptable morbidities. The physical and biological benefits of C-ions have permitted significantly shorter-course radiotherapy. References: [1] Tsujii H, Minohara S, Noda K: Heavy-particle radiotherapy: System design and application. Reviews of Accelerator Science and Technology Vol 2 (ed. by Chao AW), Imperial College Press, UK, pp1-19, 2009. [2] Tsujii H, Kamada T.: A review of update clinical results of carbon-ion radiotherapy. Jpn J Clin Oncol. 2012; 42(8): 670–685. Keywords: Carbon-ion, Radiotherapy 201 The ULICE project The ULICE Consortium The ULICE project was launched in 2009 with the aim to develop appropriate instruments for high- performance hadron-therapy (with a special attention to carbon ion therapy) and to foster the collaboration among existing and future centres, as well as between all the actors involved in this research field. ULICE is funded for four years by the European Commission with 8.4 million Euros and involves 20 European institutions coordinated by CNAO. All the existing and planned European ion therapy facilities are involved in the project, together
ICTR-PHE – 2014 with two research centres (CERN and GSI) and two industrial companies (Siemens and IBA). The project is built on 3 pillars, each coordinated by a different institution and focusing on one aspect of the composite objective pursued by the ULICE project. The first pillar is the ‘Joint Research Activities” and aims at improving the performances of hadron-therapy facilities by developing new tools and protocols. In particular, a novel adaptive treatment planning, a computer assisted programme to select the patients, as well as new protocols, would give the possibility to perform the best treatment for every tumour, possibly combining different types of irradiation. Reducing the dimensions and costs of the gantry, the structure that gives the possibility to direct the beam from any directions out of 360° degrees, is another important goal for this section of the project. The second pillar, called “Network Activities” focuses on the necessity for interaction and know-how sharing between the partners involved in the project, as well as on disseminations activities, which goes from workshop and training for researchers, to publications and outreach events. Finally, the third pillar, “Transnational Access”, aims at providing access for external users to hadron-therapy facilities in order to use the particles beam for research purposes, besides treatments. Beam time will be allocated to external researchers on the base of the impact of the proposed project, after evaluation by a dedicated review committee.
S99 and PTX3. The expression of inflammation markers and their kinetics were correlated with pts’ characteristics. Results: 20 pts were enrolled in this preliminary evaluation. All pts were treated with IMRT at 78Gy. 3/20 pts reported grade2-3 acute rectal tox. CCL2 was the most interesting marker showing significant increase during and after RT. Median values were: 127 (day 0), 135 (8Gy), 146 (50Gy), 158 (RT end), 143 (1month), 163 (6months) and 146 (12months), p range: 0.002-0.04. CCL2 levels at RT end could be modelled using linear regression including the following variables: basal CCL2 (p=0.0001), age (p=0.0013), surg (p =0.03), hypertension (p=0.006) and use of anticoagulants (p=0.03), multiple correlation coefficient=0.89 (see plot). Study of correlation between inflammation markers and acute tox was not possible, due to the low number of events. Conclusions: This preliminary study identified a correlation between CCL2 levels at the end of RT and basal CCL2, age and surg, hypertension and use of anticoagulants, suggesting a response to RT which is modulated by pts’ characteristics. Larger accrual is needed to confirm this preliminary result and to analyse its correlation with radio-induced tox.
Keywords: hadrontherapy, cancer, radiotherapy Acknowledgment: The ULICE project is co-funded by the European Commission under FP7 Grant Agreement N. 228436. 202 Mediators associated to the inflammatory response in prostate cancer patients undergoing RT: preliminary results R. Valdagni1, P. Allavena2, B. Avuzzi1, N. Bedini1, T. Magnani1, S. Morlino1, S. Pesce2, T. Rancati1, S. Villa1, N. Zaffaroni1 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Italy 2 Clinical and Research Institute Humanitas, Rozzano, Italy Purpose: A very recent “hot topic” in prostate cancer (PCa) radiotherapy (RT) is the observed association between late rectal toxicity (tox) and the presence of abdominal surgery (surg) before RT. The exact mechanism is unclear. It has been speculated that previous surgery may act throughout a limitation in blood supply and/or in reducing bowel movements. The important role that cytokines play in inflammation, fibrosis, and tissue restitution has been elucidated by Okunieff et al (2008) and some investigators have even shown that the levels of inflammatory cytokines in individual animals of the same strain affects the severity of tox from animal to animal (Liang 2003). It is also well established that patients (pts) with intrinsically high inflammatory states (e.g., collagen vascular disease, autoimmune disease) are at extremely high risk of severe fibrosis after pelvis RT (Willett 2000). Thus, we could expect that the variability of these cytokines among pts might explain the wide variability of clinical tox. Our working hypothesis was that surg may influence plasma level of inflammatory molecules and this fact might result in an enhanced radiosensitivity. We here present preliminary results on monitoring the expression of inflammatory molecules during RT. Material and Methods: Plasma levels of a panel of soluble mediators associated to the inflammatory response were measured in PCa pts undergoing RT. The blood was collected before starting RT (day 0), after 8Gy and after 50Gy, at the end of RT, at 1, 6 and 12 month followup. We measured 4 primary cytokines (IL-1, IL-6, IL-8, TNF), a chemokine (CCL2)
Keywords: Prostate inflammatory markers
cancer,
radio-induced
toxicity,
203 Moving forward in radionuclide development in Switzerland N. Van der Meulen1,2, R. Schibli1, A. Tϋrler2 1 Paul Scherrer Institut, Center of Radiopharmaceutical Science, Villigen, Switzerland 2 Paul Scherrer Institut, Laboratory of Radiochemistry and Environmental Chemistry, Villigen, Switzerland Paul Scherrer Institut (PSI), recently celebrating 25 years of existence, has been the pioneer of many radiochemical and physics projects over the years. PSI produced radionuclides commercially, such as 82Sr, but has since concentrated on radionuclide production for research purposes. PSI has recently shown interest in radionuclides such as 161Tb [1, 2], 155Tb [2, 3], 44Sc [4], 64Cu and 89Zr [5] for diagnostic and therapeutic purposes, respectively. The related research is hoping to provide proof that 161Tb can match the therapeutic value of 177Lu, while 44Sc may be more effective in diagnosis than 68Ga, again putting PSI at the forefront of nuclear medicine research with new radionuclidic possibilities. A mandate has recently been announced, prioritising nuclear medicine and it is hoped that the necessary funding can be acquired to upgrade the facilities in this regard. A number of possibilities can be provided to cement the future of PSI in the world of radionuclide production: the first would be the upgrade the current target facilities to
ICTR-PHE – 2014
Material and Methods: The Compton telescope will consist of three detector layers and each layer will be made of a continuous LaBr3 crystal coupled to four Silicon Photomultiplier (SiPM) arrays. A two layer prototype of the telescope has already been built 2
up and tested. Each layer is composed of a 32x36 mm LaBr3 crystal coupled to four SiPM arrays. The first detector (placed closer to the radioactive source) is 5 mm thick, the second one is 10 mm thick. Each SiPM array, from Hamamatsu Photonics (S11064-050P(X1)), consists of 16 (4x4) Multi Pixel Photon Counter (MPPC) with elements of 3 mm x 3 mm size, each one composed of 3600 microcells of 50 µm x 50 µm size. The MPPC arrays are placed in a custom made hybrid board that provides mechanical support, the bias for the MPPC arrays and also hosts a VATA64HDR16 ASIC from Gamma Medicas-Ideas, employed to read-out the 64 detector channels. Each hybrid board is connected to a data acquisition system (DAQ) developed at IFIC and equipped with an FPGA that provides the configuration for the ASIC and the control of the acquisition process. A third detector layer 3
of the telescope, made of a 27.2x26.8x5 mm LaBr3 crystal coupled to four SiPM arrays, has been assembled and tested. Each SiPM array consists of 16 (4x4) MPPC from Hamamatsu (S11830-3344MF), with elements of 3 mm x 3 mm size. The energy resolution obtained in the preliminary tests with the third detector layer is 6.6% FWHM at 511 keV. Results: Coincidence tests have been carried out with the two layer telescope, placing the two detectors 41 mm apart and a
22
Na source 49 mm far from the first detector. Photons 22
emitted by a Na source that are Compton scattered in the first detector and interact also in the second, have been 22
collected. Images of a Na point-like source have been reconstructed employing a ML-EM algorithm, determining the correct functioning of the prototype. Conclusions: A two layer Compton Camera with continuous LaBr3 crystals coupled to SiPM arrays has been assembled and
tested. Coincidence tests have been successfully performed and allow the reconstruction of a 22Na point-like source. Inbeam tests have been performed at the CNA (National Accelerator Center) in Seville. A cyclotron providing an 18 MeV proton beam, was used to irradiate quartz and graphite targets. The in-beam coincidence data processing is ongoing. 200 Current Status of Carbon-Ion Radiotherapy at NIRS H. Tsujii National Institute of Radiological Sciences (NIRS), Chiba, Japan Introduction: In June 1994, the NIRS initiated carbon ion radiotherapy (C-ion RT) with HIMAC that was built as a part of the nation’s “Overall 10-year anti-cancer strategy in
Japan”. Since then, the HIMAC has served as a multipurpose facility that is jointly used for cancer therapy and fundamental studies. In 2010, a new treatment building with three rooms was built to use beam lines extending from the HIMAC. This was designed to administer adaptive charged particle therapy with pencil beam scanning, as well as to develop a compact rotating gantry [1]. Treatment with the scanning method started in 2011, and its indications have since been expanded to many types of tumors [2]. Materials/Methods: Initially, phase I/II trials were performed in order to confirm the safety and efficacy of C-ion RT, with the fraction number and treatment time being fixed for each tumor. In this way, the total dose was escalated in successive increments of 5 to 10%. Consistent efforts have been made to provide C-ion RT on an ethically and scientifically sound basis under a number of Committees. Results: As of August 2013, the total number of patients registered is more than 7,700. The experiences to date indicate that C-ion RT is advantageous for the following tumors: skull base tumors, head and neck cancer (adenocarcinoma, adenoid cystic carcinoma, malignant melanoma), NSCLC (early stage, locally advanced tumors), hepatocellular cancer, pancreatic cancer, prostate cancer, rectal cancer (postoperative pelvic recurrence), bone/soft tissue sarcoma of the pelvis, paraspinal region and head/neck, and uterine cervix adenocarcinoma. Tumors located in the vicinity of critical organs such as the eye, spinal cord and digestive tract with a relatively large size and/or irregular shape have also been effectively treated. However, tumors that infiltrate or originate in the digestive tract are difficult to control with C-ion RT. Regarding dose fractionations, a significant reduction in fractions has been obtained with acceptable toxicities in most cases. For example, stage I lung cancer and liver cancer can be treated with only one or two fractions, respectively. Even for prostate cancers, 12 to16 fractions have been sufficient. Currently, the number of irradiation sessions per patient averages 12 fractions spread over approximately three weeks. Conclusions: Clinical advantages have been demonstrated in the treatment of several types of tumors with C-ions, in particular, non-squamous cell type of tumors, and locally advanced, large tumors with acceptable morbidities. The physical and biological benefits of C-ions have permitted significantly shorter-course radiotherapy. References: [1] Tsujii H, Minohara S, Noda K: Heavy-particle radiotherapy: System design and application. Reviews of Accelerator Science and Technology Vol 2 (ed. by Chao AW), Imperial College Press, UK, pp1-19, 2009. [2] Tsujii H, Kamada T.: A review of update clinical results of carbon-ion radiotherapy. Jpn J Clin Oncol. 2012; 42(8): 670–685. Keywords: Carbon-ion, Radiotherapy 201 The ULICE project The ULICE Consortium The ULICE project was launched in 2009 with the aim to develop appropriate instruments for high- performance hadron-therapy (with a special attention to carbon ion therapy) and to foster the collaboration among existing and future centres, as well as between all the actors involved in this research field. ULICE is funded for four years by the European Commission with 8.4 million Euros and involves 20 European institutions coordinated by CNAO. All the existing and planned European ion therapy facilities are involved in the project, together
ICTR-PHE – 2014 with two research centres (CERN and GSI) and two industrial companies (Siemens and IBA). The project is built on 3 pillars, each coordinated by a different institution and focusing on one aspect of the composite objective pursued by the ULICE project. The first pillar is the ‘Joint Research Activities” and aims at improving the performances of hadron-therapy facilities by developing new tools and protocols. In particular, a novel adaptive treatment planning, a computer assisted programme to select the patients, as well as new protocols, would give the possibility to perform the best treatment for every tumour, possibly combining different types of irradiation. Reducing the dimensions and costs of the gantry, the structure that gives the possibility to direct the beam from any directions out of 360° degrees, is another important goal for this section of the project. The second pillar, called “Network Activities” focuses on the necessity for interaction and know-how sharing between the partners involved in the project, as well as on disseminations activities, which goes from workshop and training for researchers, to publications and outreach events. Finally, the third pillar, “Transnational Access”, aims at providing access for external users to hadron-therapy facilities in order to use the particles beam for research purposes, besides treatments. Beam time will be allocated to external researchers on the base of the impact of the proposed project, after evaluation by a dedicated review committee.
S99 and PTX3. The expression of inflammation markers and their kinetics were correlated with pts’ characteristics. Results: 20 pts were enrolled in this preliminary evaluation. All pts were treated with IMRT at 78Gy. 3/20 pts reported grade2-3 acute rectal tox. CCL2 was the most interesting marker showing significant increase during and after RT. Median values were: 127 (day 0), 135 (8Gy), 146 (50Gy), 158 (RT end), 143 (1month), 163 (6months) and 146 (12months), p range: 0.002-0.04. CCL2 levels at RT end could be modelled using linear regression including the following variables: basal CCL2 (p=0.0001), age (p=0.0013), surg (p =0.03), hypertension (p=0.006) and use of anticoagulants (p=0.03), multiple correlation coefficient=0.89 (see plot). Study of correlation between inflammation markers and acute tox was not possible, due to the low number of events. Conclusions: This preliminary study identified a correlation between CCL2 levels at the end of RT and basal CCL2, age and surg, hypertension and use of anticoagulants, suggesting a response to RT which is modulated by pts’ characteristics. Larger accrual is needed to confirm this preliminary result and to analyse its correlation with radio-induced tox.
Keywords: hadrontherapy, cancer, radiotherapy Acknowledgment: The ULICE project is co-funded by the European Commission under FP7 Grant Agreement N. 228436. 202 Mediators associated to the inflammatory response in prostate cancer patients undergoing RT: preliminary results R. Valdagni1, P. Allavena2, B. Avuzzi1, N. Bedini1, T. Magnani1, S. Morlino1, S. Pesce2, T. Rancati1, S. Villa1, N. Zaffaroni1 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Italy 2 Clinical and Research Institute Humanitas, Rozzano, Italy Purpose: A very recent “hot topic” in prostate cancer (PCa) radiotherapy (RT) is the observed association between late rectal toxicity (tox) and the presence of abdominal surgery (surg) before RT. The exact mechanism is unclear. It has been speculated that previous surgery may act throughout a limitation in blood supply and/or in reducing bowel movements. The important role that cytokines play in inflammation, fibrosis, and tissue restitution has been elucidated by Okunieff et al (2008) and some investigators have even shown that the levels of inflammatory cytokines in individual animals of the same strain affects the severity of tox from animal to animal (Liang 2003). It is also well established that patients (pts) with intrinsically high inflammatory states (e.g., collagen vascular disease, autoimmune disease) are at extremely high risk of severe fibrosis after pelvis RT (Willett 2000). Thus, we could expect that the variability of these cytokines among pts might explain the wide variability of clinical tox. Our working hypothesis was that surg may influence plasma level of inflammatory molecules and this fact might result in an enhanced radiosensitivity. We here present preliminary results on monitoring the expression of inflammatory molecules during RT. Material and Methods: Plasma levels of a panel of soluble mediators associated to the inflammatory response were measured in PCa pts undergoing RT. The blood was collected before starting RT (day 0), after 8Gy and after 50Gy, at the end of RT, at 1, 6 and 12 month followup. We measured 4 primary cytokines (IL-1, IL-6, IL-8, TNF), a chemokine (CCL2)
Keywords: Prostate inflammatory markers
cancer,
radio-induced
toxicity,
203 Moving forward in radionuclide development in Switzerland N. Van der Meulen1,2, R. Schibli1, A. Tϋrler2 1 Paul Scherrer Institut, Center of Radiopharmaceutical Science, Villigen, Switzerland 2 Paul Scherrer Institut, Laboratory of Radiochemistry and Environmental Chemistry, Villigen, Switzerland Paul Scherrer Institut (PSI), recently celebrating 25 years of existence, has been the pioneer of many radiochemical and physics projects over the years. PSI produced radionuclides commercially, such as 82Sr, but has since concentrated on radionuclide production for research purposes. PSI has recently shown interest in radionuclides such as 161Tb [1, 2], 155Tb [2, 3], 44Sc [4], 64Cu and 89Zr [5] for diagnostic and therapeutic purposes, respectively. The related research is hoping to provide proof that 161Tb can match the therapeutic value of 177Lu, while 44Sc may be more effective in diagnosis than 68Ga, again putting PSI at the forefront of nuclear medicine research with new radionuclidic possibilities. A mandate has recently been announced, prioritising nuclear medicine and it is hoped that the necessary funding can be acquired to upgrade the facilities in this regard. A number of possibilities can be provided to cement the future of PSI in the world of radionuclide production: the first would be the upgrade the current target facilities to