IGFAE workshop on technologies and applied research at the future Galician proton-therapy facility

9 May 2023, 09:00 → 10 May 2023, 17:25 Europe/Zurich

Antonio Fernandez Prieto (Instituto Galego de Física de Altas Enerxías (IGFAE) Universidade de Santiago de Compostela (ES)), Dolores Cortina, Jose Benlliure (University of Santiago de Compostela), Pablo Vazquez (Universidade de Santiago de Compostela (ES))

 

 

The aim of this workshop is to gather and analyze interests and developments related with proton-therapy accelerators at national and international level for the next years, in a scenario where new public proton-therapy treatment and research facilities will be installed soon in Spain, and more precisely in Santiago de Compostela. Here it is a meeting point where the treatment facility will be presented to the scientific community and scientists will present their related research to the social agents. Discussion and analysis of the topics at this workshop will be steered by different perspectives.

On top of that, this workshop aims also to ignite a future network for managers, workers and users of those facilities. 

As a key speakers and contributions, we expect to count with representatives, among others, of:

• Health System and Radiotherapy treatment environment
• Technical aspects of proton-therapy infrastructures and facilities
• Scientific community with research focus on proton-therapy related developments

 

Registration for the event is open and attendance is free of fees (registration required).

Some slots for specific presentations are available. Submit your abstract now. Also, a poster session is schedule. You can select your type of contribution in the abstract submission form. 

 

Tuesday 9 May

Venue: IGFAE Director

M1: Scenario

Convener: Jose Benlliure (University of Santiago de Compostela)

1 Radioterapia de precisión: Escenario 2023

Radioterapia de precisión: Escenario 2023

Speaker: Dr Antonio Gómez Caamaño (Hospital Clínico Universitario Santiago de Compostela)

2 Impacto económico de grandes infraestructuras científicas

Speaker: María Luz Loureiro García

3 New approaches in spatio-temporal dose modulation in proton therapy.

New approaches in spatio-temporal dose modulation in proton therapy.

Speaker: Yolanda Prezado (Institut Curie)

11:00 Coffee Break

M2: Scenario

Convener: Dolores Cortina

4 CCB of IFJ PAN: an example of coexistence of hadron therapy and applied and basic research

The Cyclotron Center Bronowice (CCB) is the proton beam facility at the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) devoted mainly to conduct hadron therapy. Additionally it offers the possibility of using proton beams for nuclear physics research.
There is established experimental program based on proposals evaluated by International Advisory Committee.
In my talk I will give some information about CCB, concerning technical features and conducted proton therapy. I will also tell about nuclear physics experiments and detector tests carried out at the CCB using a proton beam from a medical cyclotron.

Speaker: Maria Kmiecik (IFJ PAN Kraków)

5 The Need for a Research Room in a Proton Therapy Center – Dresden perspective

Particle therapy (PT) has emerged as an important innovative technology for tumor treatment. It is demonstrably superior to conventional radiotherapy with MV X-rays and electrons in more and more applications and is therefore becoming increasingly important. Nevertheless, extensive research is still required to fully exploit its full potential. A better understanding of the relative biological effectiveness, the long-term consequences of the generated secondary particles (e.g. neutrons) and the range verification of the therapeutic particles are just a few selected examples of intensive research.
In addition to fundamental research at research accelerators, such clinical research is also carried out at many of the more than 100 proton therapy facilities worldwide. However, the treatment room is often unsuitable for such activities, as it is primarily designed for safe and efficient patient treatment. In addition, the available beam parameters in the treatment room are often limited in order to guarantee reliable dose application.
An additional room for clinical research makes it possible to carry out and optimize systematic long-term studies over a period of several days or weeks without influencing patient operations. A wide range of non-clinical beam parameters enables the development of technologies beyond the current state of the art.
This presentation gives an overview of the advantages of such an experimental area on the example of the OncoRay in Dresden and shows which different research topics are be worked on there.

Speaker: Toni Koegler

6 Bunker Shielding Monte Carlo Simulation for the HUMV Protontherapy Facility

The Spanish Nuclear Safety Council (CSN) demands the preparation of a Radiation Protection (RP) report by an independent entity for the commissioning of the BEAMPRO250 cyclotron machine at Valdecilla Hospital (HUMV). To meet this legal requirement, the Instituto de Física de Cantabria (IFCA) has developed a Geant4-based simulation tool that, given the machine geometry and annual workload, determines the concrete shielding conditions and the RP occupational areas according to international safety standards. The performance capability of the software package and main preliminary results that include civil engineering implications are presented here.

Speaker: Alberto Arteche (Instituto de Física de Cantabria (IFCA))

2023_05_09_IGFAE_workshop.pdf

13:00 Lunch

T: Radiobiology

Convener: Ana Vega

7 Proton Therapy beyond cancer: Potential benefits for neurodegenerative disorders

Radiotherapy (RT) is a well-established medical modality that is delivered to more than 50% of cancer patients at some point of their treatment. Additionally, RT has been successfully used to treat extra-cranial amyloidosis and current evidence indicates that is a promising treatment for amyloid-associated neurodegenerative disorders such as Alzheimer’s, Parkinson's, and Huntington's diseases. Furthermore, new modalities of RT could enhance biological effects and reduce potential toxicity.
Proton Therapy (PT) is one of the most effective techniques of external RT due to the substantial clinical advantages of protons over conventional RT based on photons or electrons. These advantages include a favorable depth dose distribution, a lower lateral spread and a minimal scatter that allows a decrease in collateral damage. This modality is currently tested in cancer settings, but it is largely untested in the context of amyloidosis and neurodegenerative disorders.
Our goal is to evaluate the capability of PT and other RT modalities to disrupt or diminish the formation of toxic protein amyloids associated with neurodegenerative disorders, bringing together fundamental nuclear physics and biochemistry. First gamma-irradiations of cell lines expressing neurodegenerative disease-associated proteins, indicated a decrease in the expression and aggregation of the pathological proteins, which was proportional to the applied dose. These results have encouraged the proposal of a PT irradiation experiment to established cell lines at the implantation beam line of the CMAM laboratory, which is currently under preparation.
In this talk, we will present the results of the gamma-irradiations, as well as the current status of the PT measurements. Our scope is to lay the groundwork for the application of PT beyond cancer, multiplying the versatility of new proton therapy facilities, and modifying the development of currently incurable neurodegenerative disorders.

Speaker: Carina Coelho (FCUL, LIP-Lisbon (NUC-RIA), BioISI)

CarinaMarquesCoelho.pdf

8 New radiobiology detector using scintillating arrays

The radiobiological experiments show that in order to make an adequate correspondance between the biological effects and the dosimetric measurements it is necessary to have a high resolution dose map (~ microns). Having this in mind a project is being developed at Laboratório de Instrumentação e Física Experimental de Partículas (LIP), in Portugal, that aims at the development of a detector to allow for the performance of radiobiology studies with high spatial resolution, real time dose measurements and tissue equivalence using scintillating optical fibres. In this talk we will explore the development of the detector, the first tests and other applications of this solution to other areas of radiotherapy (minibeam radiotherapy and Quality Assurance tasks).

Speaker: Duarte Guerreiro

DuarteGuerreiro_IGFAEworkshop.pdf

DuarteGuerreiro_IGFAEworkshop.pptx

9 Unraveling the complexities of radiation damage through Microdosimetric Kinetic Model: The role of clonogenic data in clinical RBE

DNA damage produced by ionizing radiation can be divided into two categories: lethal and sublethal lesions. Lethal lesions are those that result directly in cell death. Sublethal lesions do not result in immediate cell death but may combine to become a lethal lesion after a period or may be repaired by the cell. The spatial distribution of damage, and hence the distribution of deposited energy, is relevant in the determination of the biological effect of radiation.

The use of protons in radiotherapy has increased significantly over the last decade. Protons deposit relatively little dose along the initial stretch of their track inside matter up to a region called Bragg peak, in which a great amount of dose is released with almost no dose beyond that point. At this point, a high ionization density is found, leading to a higher local concentration of DNA damage, with increased complexity.

To compare the effect of different types of radiation, the Relative Biological Effectiveness (RBE) is defined as the ratio of the doses required to produce a given biological effect with two different types of radiation, typically using photons as the reference radiation. For proton therapy, the assumption of a constant RBE = 1.1 is the clinically accepted convention. However, existing in vitro experimental data suggest otherwise [1-4]. To potentially account for this in clinical practice, phenomenological and mechanistic models have been proposed to determine the RBE in each case, such as the Microdosimetric Kinetic Model (MKM). The MKM postulates the concept of domain as representing the maximum distance for sublethal lesions to pairwise interact to form a lethal lesion and lead to cell death. The size of the cell nucleus is also relevant to characterize how many lethal and sublethal lesions can be induced by radiation and at what point a lethal lesion is warranted from a given radiation.

Clonogenic experiments are important for this purpose because they determine the percentage of cells that keep their mitotic viability after a given irradiation. The linear-quadratic (LQ) model represents the logarithm of clonogenic survival with linear (α) and quadratic (β) dependences on the delivered dose and typically is fitted to the results from clonogenic experiments. Particle Irradiation Database Ensemble (PIDE) from the GSI, is a database that provides irradiation conditions, cell line information, andthe linear component and quadratic component parameters for different clonogenic experiments the ion used. By analyzing these experiments from exposures to protons, alpha particles, and carbon ions, two main quantities of the MKM can be obtained experiment-wise: the statistical distribution of domain radius values and the cell nucleus radius. The MKM uses these parameters to obtain the α parameter corresponding to a given radiation.

In this work, survival curves obtained from clonogenic assays were employed to determine the values of cell-specific parameters in the context of the MKM in a systematic way. This determination represents an approach to include further information on the cell line-specific radiosensitivity, which is important for proton therapy. Our results showed large variability among different cell lines, illustrating the importance of intrinsic response to radiation of different biological systems when determining RBE. The considerable deviations among groups and experiments raise the question of how valuable RBE models based on clonogenic assays are for the clinics. Also, the significant number of nuances to be considered in these models, and the lack of connection with realistic biological processes in the clinical response to radiation contribute to challenging the translatability of clonogenic survival in the clinic.

It is likely that a significant portion of the reported variability in PIDE comes from the fact that multiple institutions and laboratories carried out these experiments in different experimental conditions. Therefore, standardized methods to perform clonogenic assays for different particles and energies, especially clinical ones, may lead to better results in predicting RBE for clinical practice.

[1] Carabe A, Moteabbed M, Depauw N, Schuemann J, Paganetti H. Range uncertainty in proton therapy due to variable biological effectiveness. Phys Med Biol 2012;57:1159–72. https://doi.org/10.1088/0031-9155/57/5/1159.

[2] McNamara AL, Schuemann J, Paganetti H. A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data. Phys Med Biol 2015;60:8399–416. https://doi.org/10.1088/0031-9155/60/21/8399.

[3] McNamara A, Willers H, Paganetti H. Modelling variable proton relative biological effectiveness for treatment planning. Br J Radiol 2019;92:1–11.

[4] Wedenberg M, Lind BK, Hårdemark B, Wedenberg M, Lind BK, A BH. A model for the relative biological effectiveness of protons: The tissue specific parameter α/β of photons is a predictor for the sensitivity to LET changes. Acta Oncol (Madr) 2013;52:580–8. https://doi.org/10.3109/0284186X.2012.705892.

Speaker: Daniel Suarez-Garcia (Universidad de Sevilla)

DanielSuarezGarcia_rdPIDE_Workshop_Santiago.pdf

10 Installation of a tool based on GAMOS/Geant4 with calculation of the biological effect for the planning of CUN proton therapy treatments

Introduction: Proton therapy makes it possible to achieve coverage levels for target volumes similar to the most advanced gamma radiotherapy techniques, irradiating significantly less healthy tissue. In addition, numerous publications suggest that proton irradiation produces a high biological effect. On the other hand, Monte Carlo (MC) simulation is accepted as the most accurate tool for calculating doses in proton therapy and has been shown in various publications to be superior to commercial tools based on simplified MC. With the aim of improving the efficacy of proton therapy treatments, we have started a funded project to introduce MC planning with biological dose calculation in proton therapy treatments for CUN.

Method: In a first phase, it is necessary to adjust the parameters of the MC simulation to the CUN beam in a similar way to how it is done for the implementation of the Treatment Planning System. In the second phase, the biological effects will be introduced in the MC planning of the treatments, using the latest LEM and MKM mechanistic models, which are already in use in carbon ion therapy and will be adapted to proton therapy. In parallel, a Graphical User Interface (GUI) will be developed to allow easy use by CUN staff. The last stage will consist of a retrospective study of patients with the objective of analyzing the predictions of an increase in the Relative Biological Effect by MC, comparing them with the clinical effects in the medium and long term in patients, to identify those cases where the dose calculation biological is more necessary.

Results: Using a double Gaussian Twiss model for the spatial and angular description of the beam, we have developed a quasi-automatic method to fit the 16 model parameters for each of the 98 possible energies of the CUN beam. The adjustment with the experimental results offers values of the gamma index 1%/1mm below 0.5. Likewise, by tuning the energy and the ionization potential in water, we have adjusted the positions of the Bragg peak, achieving an agreement with the IDD measurements with values below 0.5 of the 1%/1mm gamma index. Finally, after adjusting the absolute dose and verifying the dose with various water and heterogeneous phantoms, we achieved a good agreement for complete treatments. The differences observed with the TPS are as expected given the higher precision of the MC simulation calculations.

Conclusion: We have adjusted the parameters of the MC simulation to the CUN proton therapy beam, obtaining very good agreement with the experimental data and the TPS. After introducing the prediction of biological effects, we will be able to begin the retrospective study of patients of the effect of the increase in RBE predicted by the MC calculations. In parallel, a GUI will be developed to allow its daily use in treatment planning at the CUN.

Speaker: Pedro Arce (CIEMAT - Centro de Investigaciones Energéticas Medioambientales y Tec. (ES))

IGFAE_Ciemat_CUN_SIMPROTER_BIO.pdf

11 Radiobiology studies in proton therapy: range verification with Zn nanoparticles and studies of cell surveillance after irradiation with different LETs

The unique properties of protons allow the treatment of specific areas avoiding surrounding tissues due to the deposition in depth of the dose and the different values of Linear Energy Transfer (LETs) along this deposition. The effect of protons is due to a high LET compared to the conventional radiotherapy and the relative biological effectiveness (RBE) as a function of LET is described to be different depending on the cell line. However, the large-scale clinical use of proton beam precision is hampered by the uncertainties of the location of the distal dose fall-off in the patient’s body and the different effect of radiation depending on the cell lines. In vivo verification of the delivered dose and tumor irradiation effects are two variables that are highly desirable to study for reducing systematic uncertainties in delivered dose. A promising approach to study the proton range is the use of nanoparticles as proton-activable agents that produce positron emitters which could be detected by Positron Emission Tomography (PET) and/or prompt-gamma (PG) rays. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit), studied their cytotoxicity in vitro, the production of PET/PG signals after proton irradiation and its biodistribution in vivo. In the cytotoxicity studies, we obtained the half of surveillance (IC50 values) at 64 µg Fe/ml and 100 µg Zn/ml for the U251 cell line by MTT assay. To evaluate the production of PET and PG signals, different concentrations of IONP@Zn-cit were irradiated with 10 MeV protons, obtaining negligible PET signal but PG detection at the lowest concentration measured (10 mg Zn/ml). From the biodistrubution study, IONP@Zn-cit showed a typically accumulation in liver and spleen, and an accumulation in tumor tissue of 0.95 % ID/g in a mouse model of U251 cell line.
Furthermore, to evaluate RBE with different LETs in cell cultures, a new set-up for a clinical proton irradiator was built, which allows a dose deposition with uncertainties under 9% for the less favourable cases. Moreover, cell surveillance was measured by a new method: after irradiation and growth of cells cultured in 96 well plates, cells were stained, diluted with methanol and absorbance measured as a function of seeded cells. Values were fitted to a normalized logistic function and the midpoint (number of seeded cells where the function takes 50% of its maximum signal) was used to calculate the Survival Fractions obtaining comparable results as the ones obtained with the traditional method of counting colonies in 6 well plates.
In conclusion, two different approaches are proposed to get a better knowledge on radiobiology field of proton therapy, from the range verification with nanoparticles to the in vitro study of LETs, opening different possibilities to the future in the research of proton therapy.

Speaker: Marta Ibáñez-Moragues (CIEMAT)

Presentation_v3.pdf

Presentation_v3.pptx

Wednesday 10 May

Venue: Health Minister of the Galician Regional Government, ViceChancellor of Scientific Policy & IGFAE Director

M1: Applied Research

Convener: Pablo Vazquez (Universidade de Santiago de Compostela (ES))

12 Experiments in clinical proton beams: range verification, contrast agents and FLASH

Desde el Grupo de Física Nuclear de la Universidad Complutense hemos realizado múltiples campañas de experimentación en centros clínicos de protonterapia como el Centro de Protonterapia Quironsalud, el WPE de Essen, KVI, o el Roberts Proton Therapy Center, de la Universidad de Pennsylvania.

En la charla se detallarán los principales resultados obtenidos de dichas campañas, así como los resultados de los proyectos PRONTO-CM y CAPPERAM, y se presentarán otros proyectos que se han iniciado recientemente en el campo de la radiobiología FLASH, en cuyo desarrollo se realizará un uso intensivo de instalaciones de protones clínicas.

Speaker: DANIEL SANCHEZ PARCERISA (UCM)

13 Neutron dosimetry in particle therapy facilities: status of the LINrem project

Neutrons are a highly penetrating type of radiation that can contribute significantly to the total absorbed dose in the human body. As a result, monitoring neutron dose rates is crucial in various facilities to minimize the risk of harm to workers, patients, and the public. Commercial portable neutron detectors, also known as ambient neutron dosimeters, are typically used for this purpose. However, there are concerns about the reliability of these detectors, particularly in modern facilities that produce radiation fields with high-energy contributions (E>20MeV) or complex time structures. This issue is especially relevant in medical facilities, such as proton therapy centers, where high-energy neutrons of up to 250 MeV are produced as secondary stray radiation. Furthermore, the International Commission on Radiation Units and Measurements (ICRU) recently recommended alternative definitions for operational quantities currently used for radiation protection, which will directly impact the expected performance of neutron dosimeters for energies lower than 100 eV and higher than 50 MeV. To address these concerns, the LINrem project was launched in 2018 to provide solutions that meet the new requirements for energy sensitivity and time resolution in neutron dosimetry. The project focuses on medical applications, as well as other types of facilities that require reliable neutron dosimetry. In this work, we review the technical challenges for active and time-resolved neutron dosimetry in particle therapy. We also present the status of the LINrem project and the latest experimental results in particle therapy facilities. Finally, we discuss the prospects for new development.

Speaker: Ariel Esteban Tarifeno Saldivia (Univ. of Valencia and CSIC (ES))

Atarifeno_IGFAE_PT2023_LINrem_LR_final.pdf

14 Role and challenges of PET imaging in proton therapy

Proton therapy is the most precise external radiotherapy modality offering better dose distribution (exact-precision dosimetry, i.e., precise radiation dose and location) and, as a result, less radioactivity exposure to healthy tissues and a lower likelihood of unneeded radioinduced side effects.
The fact that protons have a limited range when they enter the body is one of the key benefits of proton treatment. The energy of the proton beam and the physical properties of the biological tissue they pass through—primarily the atomic number and density—determine that range. Additionally, protons deposit the majority of their energy where they stop (Bragg peak), in contrast to photon treatment. It is feasible to tailor proton irradiation to the tumor's volume by adjusting the proton beam's energy. This situation is ideal since the irradiation does not affect the tissue beyond the range of the protons. However, if a little error is made in the range estimate or proton therapy planning, irreparable harm will result and, in the worst case, affecting to a vital organ neighbor to the tumor.
Several positron emitters are created in the living tissue during proton therapy irradiation as a result of proton interactions. Therefore, positron emission tomography (PET) cameras may be used to detect the photons released from the positron radioisotopes produced and create an image of the radioactivity generated, assisting in determining whether the calculated proton range was correct. In order to quantify the activity before it decays, it is crucial that the image be captured for this purpose as soon as possible and in the same location as the patient when they were exposed to radiation.
Nowadays and in this context, our group is developing a PET system with open geometry to avoid interfering with the proton treatment beam. Specifically, we are developing a two-paddle PET device with a detection area of 256x256 mm2 among which the patient will be located. Open geometries introduce severe elongation artifacts in the images due to the lack of angular information. This contribution will show the challenges we face and the direction of our research to overcome them in the field of detector development and time-of-flight determination, as well as image reconstruction techniques.

Speaker: Dr Laura Moliner (i3M)

Role and challenges of PET imaging in proton v1.pdf

Role and challenges of PET imaging in proton v1.pptx

15 Proton acceleration and detection for clinical and preclinical research

Research at the Institute for Instrumentation in Molecular Imaging (i3M, Valencia) is related to the development of diagnostic systems and clinical or preclinical applications of nuclear physics techniques. We present two recent advances related to particle therapy. The necessity for online range measurement for the real-time determination of the position of the Bragg peak has been much discussed throughout the last decade. We have developed a beam trigger detector based on scintillating fibres which can be used for precise coincidence timing at clinical beam intensities and thereby allows for background suppression in prompt-gamma detection and spectroscopy. Tests with an upgrade version are ongoing.
The second research topic relies on proton and ion acceleration with ultra-short laser pulses. This type of radiation sources generate ultra-intense particle bunches and have attracted much attention as a tool for investigating radiobiological effects in the ultra-high dose rate (UHDR) regime. In close collaboration with IGFAE we have built an experimental arrangement for the irradiation of cell cultures with protons of about 5 MeV at the Laser Laboratory for Acceleration and medical Applications (L2A2, Santiago de Compostela). Our aim is to perform systematic studies of the cellular response to damage caused by different types of ionizing radiation (protons, x-rays) and their comparison to clinical radiation fields. This requires, among others, the measurement of the total dose deposition at ultra-high dose rates. First tests have been performed with a laser-based x-ray source using cell samples prepared and analysed by the Fundación Pública Galega de Medicina Xenómica (FPGMX, Santiago de Compostela).

Speaker: Michael Seimetz (Instituto de Instrumentación para Imagen Molecular (I3M))

IGFAE_Workshop_Seimetz.pdf

16 Computational and experimental methods applied for treatment planning, quality assurance, and research at the clinically operating proton-therapy facility

In this contribution, I will review technologies and applied translational research activities ongoing at the R&D lab of the Cyclotron Centre Bronowice (CCB), proton therapy center in Krakow, Poland. I will show examples of clinical translation of developed technologies to routine proton treatment planning and quality assurance (QA). Individual projects presented here have been conducted in close international collaborations with research partners, a.o., PSI and Maastro Clinic proton centers, the Sapienza University of Rome, and TIFPA (Italy), as well as commercial partners.

To support the clinical operation of the CCB proton center, we commissioned computational methods based on Monte Carlo simulations in GATE/Geant4 running on a computational cluster and GPU-accelerated proton dose engine FRED. For both codes, we developed and automated advanced proton beam modeling and validated the physics models against measurements [1]. Prospectively, FRED and GATE are used for the evaluation of LET and variable RBE distributions in proton treatment plans. Thanks to its excellent time performance, FRED is now integrated into the clinical environment to support and eventually replace patient QA measurements, while the spared QA beamtime can be used for patient treatments [2]. Since the R&D lab is in the clinical environment, we established a large database of patients treated in Krakow to study physical and biological range uncertainties in patients and new treatment planning protocols [3,4]. To verify the simulations, we employ quantum sensitive pixelated detectors TimePix (ADVACAM) for measuring dose and LET in a water phantom with single particle sensitivity [5,6]. Further research activities conducted in the proton center R&D lab include the development of a proton beam range monitoring system based on a PET detector built from plastic scintillators (J-PET technology) [7,8], prompt gamma measurements, investigation of non-clinical irradiation conditions with low and flash dose rates, development of new proton treatment plan optimization techniques, as well as nano-scale approaches to biologically weighted treatment planning [9].

[1] Gajewski et al. 2021 https://doi.org/10.3389/fphy.2020.567300
[2] Krzempek et al. 2023 (see PTCOG 61 oral presentation)
[3] Garbacz et al. 2021 M. Garbacz, https://doi.org/10.1016/j.radonc.2021.08.015
[4] Garbacz et al. 2022 https://doi.org/10.1186/s13014-022-02022-5
[5] Stasica et al. 2020 https://doi.org/10.3389/fphy.2020.00346
[6] Stasica et al. 2023 (under review in PMB)
[7] Borys et al. 2022 https://doi.org/10.1088/1361-6560/ac944c
[8] Brzezinski et al. 2023 (under review in PMB)
[9] Rucinski et al. 2021 https://doi.org/10.1088/1361-6560/ac35f1

Speaker: Antoni Rucinski

Rucinski.pdf

11:15 Coffee Break

M2: Treatment Monitoring

Convener: Antonio Fernandez Prieto (Instituto Galego de Física de Altas Enerxías (IGFAE) Universidade de Santiago de Compostela (ES))

17 A New Strategy for Range Verification in Proton Therapy: the Coaxial Approach

Eight years ago, the milestone of first-in-human range verification of a proton therapy treatment using prompt gamma-rays was achieved using a collimated gamma-ray camera. Despite being developed by a major proton accelerator vendor, the widespread clinical application and commercial availability of this device is not yet in sight. It remains unsure whether its size and weight will allow their integration on every treatment room worldwide.
To address this shortcoming, a new method without collimation was recently proposed: the monitoring of prompt gamma-rays with a single detector, coaxial to the proton beam, behind the treated area. This orientation exploits the solid angle effect, as the number of gamma-rays reaching the detector will increase in case of an overshoot, or decrease in case of an undershoot.
By solely counting the number of detections per proton, one would be able to identify range deviations with respect to the treatment plan. With this compact and affordable method, the integration in the treatment room would be facilitated compared to the state-of-the-art collimated gamma-ray cameras.
Nonetheless, this novel orientation entails unexplored challenges, namely high count rates and large neutron background in forward direction.
We report on initial developments of a demonstrator system specifically tailored to cope with up to 10 million counts per second. It comprises a cerium bromide scintillator coupled to a photomultiplier tube and a fast digitizer. First experimental tests show the ability of acquiring continuous waveforms at 2.5 GSPS without any dead time during a time span typical of a clinical treatment field, which in turn allows for a sophisticated decomposition of pile-up events. Dedicated photomultiplier supply electronics able to sustain high count rate variations have been designed with the help of behavioral circuit simulations and are being tested with controlled light sources. In parallel, detailed Monte Carlo simulations of the detector and photomultiplier tube are under development. During the next year, we plan to conduct first tests at a bremsstrahlung beam and at a clinical proton beam to obtain the first experiment proof-of-principle of coaxial detection for proton therapy range verification.

Speaker: FERNANDO HUESO GONZALEZ

Talk.pdf

18 Monitoring proton therapy treatments with in-beam positron emission tomography or with a multislat prompt-gamma camera: simulation results

Proton therapy (PT) treatments still offer space for improvement. This
is because the
positioning of the Bragg peak may still suffer from several dose
disturbing mechanisms such
as patient mispositioning and/or anatomical modifications occurring in
the course of
fractionated PT. Some examples will be covered, together with two
techniques aiming each
at the verification of each PT treatment: in-beam positron emission
tomography and
prompt gamma imaging, here simulated in the case of an orthogonal prompt
gamma ray
detection via a multi-slat collimator.

Speaker: Paulo Crespo (LIP)

PCrespo_compostela23.pdf

19 MACACO imaging system for hadron therapy treatment monitoring.

The IRIS group of IFIC is developing a system for hadron therapy treatment monitoring through the detection of the photons emitted by the irradiated tissue. The system is composed of three planes of LaBr3 crystals coupled to SiPM arrays and operated in time coincidence. After the successful results obtained with the second prototype, MACACO II, the system performance has been improved.

The performance improvement is carried out through the development of two new prototypes with different characteristics. On one hand MACACO III has improved spatial resolution through the use of new photodetectors, and its three detector planes are operated with a single readout board, the AliVATA readout system driving the VATA64HDR16 ASIC from Ideas. On the other hand, MACACOp employs the TOFPET2 ASIC from PETSys to achieve enhanced timing resolution, dynamic range and readout speed. Improved data analysis through the use of neural networks for event selection, and image reconstruction methods to combine data obtained by the different detector pairs or all three detectors are applied to both prototypes.

The two systems have been tested at the Spanish National Accelerator Centre (CNA, Sevilla) and also in two protontherapy centres. At CNA an 18 MeV proton beam irradiated a graphite target which was moved in 1 mm steps, producing 4.4 MeV photons. Both systems were able to distinguish 1 mm variations in the reconstructed photon distribution produced at different target positions.
In the Krakow protontherapy centre, a solid water (RW3) phantom was irradiated with 90 MeV protons. The energy has been varied to 88.38 and 91.62 MeV in order tp produce +-2 mm range shifts. Also in both cases, such shifts were successfully detected by the system. In the tests at Quironsalud protontherapy centre (Madrid), with a modern accelerator that imposes more challenging conditions, imaging the photon distribution at 70 MeV proton beam was also possible.

Speaker: Gabriela Llosa Llacer (Univ. of Valencia and CSIC (ES))

Llosa_IGFAEWorkshop.pdf

20 Online beam monitoring detector for FLASH irradiations

Introduction: FLASH effect is deeply influenced by the beam pulse structure (instantaneous dose-rate, dose-per-pulse or number of pulses) as it modifies the cell’s exposure to free radicals, so fast and accurate monitoring of the time structure of the beam is vital for FLASH treatments [1]. However, high dose rate plans or very short proton bunches may pose problems to current beam monitor systems. Therefore, there is an increasing demand for real-time proton beam monitoring with high temporal resolution, extended dynamic range and radiation hardness. In this context, plastic scintillators coupled to optical fiber sensors have great potential to become a practical solution towards clinical implementation. In this work, we evaluate the capabilities of a very compact fast plastic scintillator with an optical fiber readout by a SiPM and electronics sensor which has been used to provide information on the time structure at the nanosecond level of a clinical proton beam [3].
Materials and methods: A 3 × 3 × 3 mm^3 plastic scintillator (EJ-232Q Eljen Technology) coupled to a 3 × 3 mm^2 SiPM (MicroFJ-SMA-30035, Onsemi) has been characterized with a 70 MeV clinical proton beam accelerated in a Proteus One synchrocyclotron at Quironsalud protontherapy center (Madrid). The signal was read out by a high sampling rate oscilloscope (5 GS/s). By exposing the sensor directly to the proton beam, the time beam profile of individual spots was recorded.
Results: Measurements of detector signal have been obtained with a time sampling period of 0.8 ns. Proton bunch period (16 ns), spot (10 μs) and interspot (1 ms) time structures could be observed in the time profile of the detector signal amplitude.
Conclusions: The proposed system was able to measure the fine time structure of a clinical proton accelerator online and with sub-ns time resolution. The system will be tested next in an X-ray based preclinical irradiator with FLASH capabilities [4]. Its potential to measure absolute dose is also being studied.

[1] Espinosa-Rodriguez A, et al. Int J Mol Sci. 2022;23(21):13484
[2] Gómez F, et al Med Phys. 2022;49(7):4705-4714
[3] Díez, M. G., et al Med Phys 2023, 1-7
[4] Espinosa-Rodriguez, et al Radiat. Phys. Chem. 2023, 206: 110760.

Speaker: Dr Paula Ibáñez (Universidad Complutense de Madrid)

Presentación-IGFAE-PIbanez.pdf

Presentación-IGFAE-PIbanez.pdf

Presentación-IGFAE-PIbanez.pptx

21 Proton range verification using protoacoustics and artificial intelligence

The thermoacoustic pressure waves generated by the proton beam in protontherapy treatments may provide information on the distribution of the deposited dose in tissues. This approach, called protoacoustics, is a promising method for proton range verification. In this work, we show with realistic simulations and artificial intelligence models how to estimate the Bragg peak (BP) location from the measured acoustic signals.

Dose calculations were performed with the open-source treatment planning system matRad, while k-Wave was used for simulating the acoustic wave propagation in 3D. A neural network (ProtoNN) was trained to estimate the Bragg peak (BP) location for each beamspot of the treatment plan from the protoacoustic measurements. The trained ProtoNN estimates the location of the Bragg peak with precision better than 1mm in less than 100ms. This may be used to generate an alert in real-time if a significant deviation from the treatment plan is found.

Plans to verify these results with experimental measurements, as well as technical challenges and opportunities in this field will be also discussed.

Speaker: Prof. JOAQUIN LOPEZ HERRAIZ (Grupo de Fisica Nuclear e IPARCOS. Universidad Complutense de Madrid)

PROTOACOUSTICS_UCM_WORKSHOP_SANTIAGO_2023.pdf

13:25 Lunch

T: Treatment Monitoring

Convener: Paulo Crespo (LIP)

22 PET range verification in proton therapy (research at U. Sevilla and CNA)

In proton therapy, Positron Emission Tomography (PET) range verification, which is based on the detection of the short-lived (online monitoring) or the long-lived (offline monitoring) β+ emitters produced in the body of the patient, has been proved to be a well-suited technique to monitor the beam range. This technique requires the comparison of the observed activity distribution with Monte Carlo simulations, wich use as input the geometry of the patient and the detailed cross sections up to 200 MeV of the reactions resulting in the relevant β+ emitters. These are, mainly: 10C, 11C, 12N, 13N, 15O 29P and 38mK.

At Universidad de Sevilla and the Centro Nacional de Aceleradores (CNA), a new research line has been established to contribute to the implementation of PET range verification in proton therapy. The initial activities involved a series of experiments at CNA (Seville, Spain), WPE (Essen, Germany) and HIT (Heidelberg, Germany) to measure the complete set of reaction cross sections of interest, providing the first data ever for some reactions. Furthermore, in the framework of a collaboration with IFIC (C. Domingo et al.), actual β+ activity profiles resulting from irradiation of phantoms with proton clinical beams at HIT have been measured using the i-TED detection system as a PET scanner. Last, Monte Carlo simulations are being developed to assess the impact of the new data and establish the positron emitters mor relevant for the different implementations of PET range verification: on-line, in-room and off-line.

Speaker: Carlos Guerrero Sanchez (Universidad de Sevilla (ES))

CGuerrero_USC_WorkshopProtonTherapy_May2023_local.pdf

CGuerrero_USC_WorkshopProtonTherapy_May2023_local.pptx

23 On-the-fly reconstruction of activation by proton beams using in-beam PET

Introduction: In-beam PET is attractive in terms of feedback-time of treatment quality in protontherapy. However, it is challenged by the high rates produced during the beam-on period. In this work, we report the first results using a novel in-beam portable PET system that can detect and process on-the-fly the β$^+$ activity produced during and after irradiation.
Methods: The specific PET setup consisted of 6 phoswich detector blocks with 338 pixels each, with of 1.55$\times$1.55$ \times $LYSO (7mm)+GSO (8mm) . The system was coupled to a fast data acquisition system able to sustain rates up to 10 Msingles/sec. Two different PMMA targets were irradiated with mono-energetic clinical proton beams at the Quirónsalud proton therapy center.
Results: The radionuclide-specific contribution ($^{11}$C, $^{15}$O, $^{10}$C) was obtained from the time-activity curves corresponding to the irradiated region. 3D maps of the activity were reconstructed on-the-fly every 0.5 seconds and with a 0.5 mm spatial resolution (Figure 2). We also assessed the system response to changes in the position and direction of the beam during irradiation.
Conclusion: This validates the experimental setup to be used for in-beam on-the-fly reconstruction of the 3D activity when irradiating with proton beams and provides a gold standard to obtain the deposited dose distribution when combined with a fast dose reconstruction method.

Speaker: ANDREA ESPINOSA RODRÍGUEZ Not Supplied

Charla_IGFAEWorkshop_v1.pdf

Charla_IGFAEWorkshop_v1.pptx

24 A dedicated dual-head TOF-PET system for in-vivo quality control of beam delivery in proton therapy

We are developing a prototype dual-head time-of-flight (TOF)-PET system for in-vivo verification of beam delivery in proton therapy. Such a system will allow PET image acquisition shortly after irradiation, profiting from imaging of short-lived O-15 and reduced biological washout effects, whereas TOF-PET reduces image degradation due to incomplete acquisition of projection data from the planar detectors. Our proposed detector has a modular design with two parallel planar heads of approximately 20 cm by 20 cm active area, each consisting of 8 x 8 detector modules, composed of a LYSO:Ce array of 3.14 mm x 3.14 mm x 20 mm elements, optically coupled to SiPM arrays with TOF-enabling HRFlexToT ASIC readout [1]. The expected performance of the detector has been assessed via realistic Monte Carlo simulations of anonymized real patient treatments, by comparing the PET images from the original treatment with images obtained with artificially-modified proton ranges. Using a range estimation method developed by our group, we have concluded that the proposed PET system is capable of identifying range differences of the order of 1 mm with over 80% specificity and specificity, and 100% for range variations of 2 mm or larger [2-3]. We are presently developing a small field of view prototype with two planar heads of 10 cm by 10 cm to validate the proposed PET detector design.

[1] D. Sánchez, IEEE TRPMS 6 (2022) 51-67.
[2] P. Rato Mendes et al., Radioter Oncol 161 Suppl.1 (2011) S1286. [3] P. Arce et al., presented at 2022 IEEE NSS MIC.

Speaker: Pedro Arce (CIEMAT - Centro de Investigaciones Energéticas Medioambientales y Tec. (ES))

IGFAE_Ciemat_CUN_SIMPROTER_PET.pdf

25 Hybrid Compton-PET imaging for ion-range monitoring in hadron therapy

In this contribution I will present a summary of the research that we are doing at the Gamma-Ray Spectroscopy and Neutrons Group of IFIC (CSIC-UV) aimed at developing a new gamma-ray imaging methodology for enhanced accuracy ion-range verification in hadron-therapy treatments.
Two of the most promising methodologies for in-room real-time ion-range monitoring are positron-emission tomography (PET) and prompt-gamma imaging (PGI). Owing to the prompt-nature of the emitted radiation, range verification via PGI is well suited for real-time monitoring [Ler22], whereas PET imaging can provide tomographic and functional information relevant to study physiological processes and tumor response.
The method that we have implemented is based on the hybrid combination of both PGI and PET within the same system [Bal22], thus exploiting the advantages of them both. This is accomplished by means of an array of four Compton cameras in a twofold front-to-front configuration operating in synchronous mode. A summary of proof-of-concept experiments performed at CNA-Sevilla and at HIT-Heidelberg will be presented. I will finish my presentation with a short outlook about our future plans.

[Ler22] J. Lerendegui-Marco et al., “Towards machine learning aided real-time range imaging in proton therapy”, Sci Rep 12, 2735 (2022). https://doi.org/10.1038/s41598-022-06126-6

[Bal22] J. Balibrea-Correa et al., “Hybrid in-beam PET- and Compton prompt-gamma imaging aimed at enhanced proton-range verification”, The Eur. Phys. Jour. Plus, Volume 137, Issue 11, article id.1258 (2022) https://doi.org/10.1140/epjp/s13360-022-03414-y

Speaker: Cesar Domingo Pardo (Univ. of Valencia and CSIC (ES))

igfae_cdp_shortVersion.pdf

igfae_cdp_shortVersion.pptx

Closing

Convener: Jose Benlliure (University of Santiago de Compostela)