Ion Beam Therapy Research Articles

Optimization of synchrotron based ion beam therapy facilities for treatment time reduction, options and the MedAustron development roadmap.

A faster treatment reduces the risk of intra-fraction movement of organs, offers a more comfortable treatment to the patient, allows to treat lesion of larger volumes in a reasonable time and most of all expands the capacity of the facility. This work presents possible machine upgrades for synchrotron based ion beam therapy centers to shorten the irradiation time. The expected delivery times for each scenario are simulated for the study case of proton beams of MedAustron. The second part of the work focuses on the MedAustron development roadmap, where recently increase of ring fillings and delivered intensities were implemented for proton treatments achieving an average irradiation time of ~50% since start of operation.

Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques.

Simple SummaryAlthough particle therapy using protons and heavier ions has many inherent advantages when compared to x-rays for cancer treatment, numerous unknowns still exist in the radiobiology of particle therapy. Informative high-accuracy biological effects data are lacking and difficult to obtain. This study aimed to provide a novel high-throughput experimental method to more efficiently obtain large amounts of biophysical data of particle therapy and to correlate the biological responses with the physical characteristics of particle beams.Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific.

Patient-specific CT calibration based on ion radiography for different detector configurations in 1H, 4He and 12C ion pencil beam scanning

The empirical conversion of the treatment planning x-ray computed tomography (CT) image to ion stopping power relative to water causes dose calculation inaccuracies in ion beam therapy. A patient-specific calibration of the CT image is enabled by the combination of an ion radiography (iRad) with the forward-projection of the empirically converted CT image along the estimated ion trajectories. This work investigated the patient-specific CT calibration for list-mode and integration-mode detector configurations, with reference to a ground truth ion CT (iCT) image. Analytical simulations of idealized carbon ion and proton trajectories in a numerical anthropomorphic phantom and realistic Monte Carlo simulations of proton, helium and carbon ion pencil beam scanning in a clinical CT image of a head-and-neck patient were considered. Controlled inaccuracy and noise levels were applied to the calibration curve and to the iRad, respectively. The impact of the selection of slices and angles of the iRads, as well as the choice of the optimization algorithm, were investigated. Accurate and robust CT calibration was obtained in analytical simulations of straight carbon ion trajectories. Analytical simulations of non-straight proton trajectories due to scattering suggested limitations for integration-mode but not for list-mode. To make the most of integration-mode, a dedicated objective function was proposed, demonstrating the desired accuracy for sufficiently high proton statistics in analytical simulations. In clinical data the inconsistencies between the iRad and the forward-projection of the ground truth iCT image were in the same order of magnitude as the applied inaccuracies (up to 5%). The accuracy of the CT calibration were within 2%–5% for integration-mode and 1%–3% for list-mode. The feasibility of successful patient-specific CT calibration depends on detector technologies and is primarily limited by these above mentioned inconsistencies that slightly penalize protons over helium and carbon ions due to larger scattering and beam spot size.

Carbon Ion Therapy Inhibits Esophageal Squamous Cell Carcinoma Metastasis by Upregulating STAT3 Through the JAK2/STAT3 Signaling Pathway.

Radiation therapy is an important component of the comprehensive treatment of esophageal cancer. However, conventional radiation resistance is one of the main reasons for treatment failure. The superiority of heavy ion radiation in physics and biology has been increasingly highlighted in radiation therapy research. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway plays an important role in the occurrence, development and metastasis of esophageal squamous cell carcinoma (ESCC) and is related to the development of resistance to ionizing radiation in ESCC. Therefore, the aim of the present study was to investigate the relationship between carbon ion inhibition of the proliferation and metastasis of esophageal carcinoma cells and the JAK2/STAT3 signaling pathway. The results demonstrated that carbon ion beams significantly reduced cell viability and stimulated apoptosis in human ESCC cells in a dose-dependent manner. In addition, carbon ion beams induced G2/M phase cell cycle arrest in ESCC cells and inhibited tumor metastasis in a dose-dependent manner. Additionally, poorly differentiated KYSE150 cells were more sensitive to the same carbon ion beam dose than moderately differentiated ECA109 cells. Carbon ion beam exposure regulated the relative expression of metastasis-related molecules at the transcriptional and translational levels in ESCC cells. Carbon ion beams also regulated CDH1 and MMP2 downstream of the STAT3 pathway and inhibited ESCC cell metastasis, which activated the STAT3 signaling pathway. This study confirmed the inhibition of cell proliferation and the metastatic effect of carbon ion beam therapy in ESCC cells.

PO-1410: Trend lines on patient specific quality assurance in ion beam therapy with protons and carbon ions

PO-1410: Trend lines on patient specific quality assurance in ion beam therapy with protons and carbon ions

OC-0577: Impact of beamline-specific particle energy spectra on clinical plans in carbon ion beam therapy

OC-0577: Impact of beamline-specific particle energy spectra on clinical plans in carbon ion beam therapy

Characterizing Radiation Effectiveness in Ion-Beam Therapy Part II: Microdosimetric Detectors

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modelling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical beams of protons and carbon ions, the lineal-energy parameters are correlated to the clinical concept of Linear Energy Transfer (LET) and RBE. The possibilities of applying experimental microdosimetry in ion-beam therapy are discussed considering the consolidated irradiation characteristics as well as the most recent developments.

Back to the Future: Helium Ion Therapy 2020

Helium ions (4He) remained clinically unexploited worldwide since the shutdown of the clinical trials at the Lawrence Berkeley Laboratory (LBL) despite their favorable physical and biophysical characteristics. 4He afford minimal lateral scattering compared to protons, with a significantly reduced fragmentation tail compared to carbon ions and enhancement of bio-effects with relative biological effectiveness (RBE) values ranging between 1.3 and ∼3. Here, we outline milestones and on-going preparations for 4He clinical trials set for this year at our facility. Investigation of physical and biological phenomena of 4He was performed. Dosimetry was conducted in both homogenous and heterogenous (clinical-like) settings, verifying prediction of the first (non-clinical) 4He Monte Carlo (MC) and GPU-accelerated based treatment planning system (gTPS). Towards translation in patients, these systems are supporting development and integration of the first clinical treatment planning system. Additionally, in vitro, in vivo and in silico biological studies were carried out to establish robust prediction of biological effects for 4He. Prescription doses, fractionation schemes, tissue radio-sensitivity (α/βx) assignment, algorithm for effective dose calculation, and RBE model were selected for the upcoming clinical trials using 4He. In water and in anthropomorphic head phantoms, measurements yielded dose values within ∼2% against MC and gTPS predictions. For RBE modeling, measured RBE in vitro and in vivo indicates clinically relevant uncertainty of ±5-10% across different RBE model as a function of the various endpoints (dose, linear energy transfer and tissue type). Based on improved performance in the studied cell lines and tissues, as well as its accessibility in the literature, the modified microdosimetric kinetic model (mMKM) was selected as the clinical model for 4He RBE prediction. Through interdisciplinary collaboration between physicians, physicists and radiobiologists, we have addressed the prospective challenges and clinical decisions necessary for translating active scanning 4He to the clinic. Developed physical/biological models were successfully integrated in both research and commercial systems and validated against in vitro/in vivo experimental data. Together, these efforts mark an important step towards clinical translation 4He ion-beam therapy with state-of-the-art technologies.

The 20th Gray lecture 2019: health and heavy ions.

ObjectiveParticle radiobiology has contributed new understanding of radiation safety and underlying mechanisms of action to radiation oncology for the treatment of cancer, and to planning of radiation protection for space travel. This manuscript will highlight the significance of precise physical and biologically effective dosimetry to this translational research for the benefit of human health.This review provides a brief snapshot of the evolving scientific basis for, and the complex current global status, and remaining challenges of hadron therapy for the treatment of cancer. The need for particle radiobiology for risk planning in return missions to the Moon, and exploratory deep-space missions to Mars and beyond are also discussed.MethodsKey lessons learned are summarized from an impressive collective literature published by an international cadre of multidisciplinary experts in particle physics, radiation chemistry, medical physics of imaging and treatment planning, molecular, cellular, tissue radiobiology, biology of microgravity and other stressors, theoretical modeling of biophysical data, and clinical results with accelerator-produced particle beams.ResultsResearch pioneers, many of whom were Nobel laureates, led the world in the discovery of ionizing radiations originating from the Earth and the Cosmos. Six radiation pioneers led the way to hadron therapy and the study of charged particles encountered in outer space travel. Worldwide about 250,000 patients have been treated for cancer, or other lesions such as arteriovenous malformations in the brain between 1954 and 2019 with charged particle radiotherapy, also known as hadron therapy. The majority of these patients (213,000) were treated with proton beams, but approximately 32,000 were treated with carbon ion radiotherapy. There are 3500 patients who have been treated with helium, pions, neon or other ions. There are currently 82 facilities operating to provide ion beam clinical treatments. Of these, only 13 facilities located in Asia and Europe are providing carbon ion beams for preclinical, clinical, and space research. There are also numerous particle physics accelerators worldwide capable of producing ion beams for research, but not currently focused on treating patients with ion beam therapy but are potentially available for preclinical and space research. Approximately, more than 550 individuals have traveled into Lower Earth Orbit (LEO) and beyond and returned to Earth.ConclusionCharged particle therapy with controlled beams of protons and carbon ions have significantly impacted targeted cancer therapy, eradicated tumors while sparing normal tissue toxicities, and reduced human suffering. These modalities still require further optimization and technical refinements to reduce cost but should be made available to everyone in need worldwide. The exploration of our Universe in space travel poses the potential risk of exposure to uncontrolled charged particles. However, approaches to shield and provide countermeasures to these potential radiation hazards in LEO have allowed an amazing number of discoveries currently without significant life-threatening medical consequences. More basic research with components of the Galactic Cosmic Radiation field are still required to assure safety involving space radiations and combined stressors with microgravity for exploratory deep space travel.Advances in knowledgeThe collective knowledge garnered from the wealth of available published evidence obtained prior to particle radiation therapy, or to space flight, and the additional data gleaned from implementing both endeavors has provided many opportunities for heavy ions to promote human health.

A High-Granularity Digital Tracking Calorimeter Optimized for Proton CT

A typical proton CT (pCT) detector comprises a tracking system, used to measure the proton position before and after the imaged object, and an energy/range detector to measure the residual proton range after crossing the object. The Bergen pCT collaboration was established to design and build a prototype pCT scanner with a high granularity digital tracking calorimeter (DTC) used as both tracking and energy/range detector. In this work the conceptual design and the layout of the mechanical and electronics implementation, along with a Monte Carlo (MC) simulation of the new pCT system are reported. The DTC is a multilayer structure with a lateral aperture of 27 cm × 15 cm, made of 41 detector/absorber sandwich layers (calorimeter), with aluminum (3.5 mm) used both as absorber and carrier, and 2 additional layers used as tracking system (rear trackers) positioned downstream of the imaged object; no tracking upstream the object is included. The rear tracker’s structure only differs from the calorimeter layers for the carrier made of ~200 μm carbon fleece and carbon paper (carbon-Epoxy sandwich), to minimize scattering. Each sensitive layer consists of 108 ALPIDE chip sensors (developed for ALICE, CERN) bonded on a polyimide flex and subsequently bonded to a larger flexible printed circuit board. Beam tests tailored to the pCT operation have been performed using high-energetic (50–220 MeV/u) proton and ion beams at the Heidelberg Ion-Beam Therapy Center (HIT) in Germany. These tests proved the ALPIDE response independent of occupancy and proportional to the particle energy deposition, making the distinction of different ion tracks possible. The read-out electronics is able to handle enough data to acquire a single 2D image in few seconds making the system fast enough to be used in a clinical environment. For the reconstructed images in the modeled MC simulation, the water equivalent path length error is lower than 2 mm, and the relative stopping power accuracy is better than 0.4%. Thanks to its ability to detect different types of radiation and its specific design, the pCT scanner can be employed for additional online applications during the treatment, such as in-situ proton range verification.

Carbon ion radiotherapy as definitive treatment in non-metastasized pancreatic cancer: study protocol of the prospective phase II PACK-study

BackgroundRadiotherapy is known to improve local tumor control in locally advanced pancreatic cancer (LAPC), although there is a lack of convincing data on a potential overall survival benefit of chemoradiotherapy over chemotherapy alone. To improve efficacy of radiotherapy, new approaches need to be evolved. Carbon ion radiotherapy is supposed to be more effective than photon radiotherapy due to a higher relative biological effectiveness (RBE) and due to a steep dose-gradient making dose delivery highly conformal.MethodsThe present Phase II PACK-study investigates carbon ion radiotherapy as definitive treatment in LAPC as well as in locally recurrent pancreatic cancer. A total irradiation dose of 48 Gy (RBE) will be delivered in twelve fractions. Concurrent chemotherapy is accepted, if indicated. The primary endpoint is the overall survival rate after 12 months. Secondary endpoints are progression free survival, safety, quality of life and impact on tumor markers CA 19–9 and CEA. A total of twenty-five patients are planned for recruitment over 2 years.DiscussionRecently, Japanese researches could show promising results in a Phase I/II-study evaluating chemoradiotherapy of carbon ion radiotherapy and gemcitabine in LAPC. The present prospective PACK-study investigates the efficacy of carbon ion radiotherapy in pancreatic cancer at Heidelberg Ion Beam Therapy Center (HIT) in Germany.Trial registrationThe trial is registered at ClinicalTrials.gov: NCT04194268 (Retrospectively registered on December, 11th 2019).

Clinical Radiobiology of Fast Neutron Therapy: What Was Learnt?

Neutron therapy was developed from neutron radiobiology experiments, and had identified a higher cell kill per unit dose and an accompanying reduction in oxygen dependency. But experts such as Hal Gray were sceptical about clinical applications, for good reasons. Gray knew that the increase in relative biological effectiveness (RBE) with dose fall-off could produce marked clinical limitations. After many years of research, this treatment did not produce the expected gains in tumour control relative to normal tissue toxicity, as predicted by Gray. More detailed reasons for this are discussed in this paper. Neutrons do not have Bragg peaks and so did not selectively spare many tissues from radiation exposure; the constant neutron RBE tumour prescription values did not represent the probable higher RBE values in late-reacting tissues with low α/β values; the inevitable increase in RBE as dose falls along a beam would also contribute to greater toxicity than in a similar megavoltage photon beam. Some tissues such as the central nervous system white matter had the highest RBEs partly because of the higher percentage hydrogen content in lipid-containing molecules. All the above factors contributed to disappointing clinical results found in a series of randomised controlled studies at many treatment centres, although at the time they were performed, neutron therapy was in a catch-up phase with photon-based treatments. Their findings are summarised along with their technical aspects and fractionation choices. Better understanding of fast neutron experiments and therapy has been gained through relatively simple mathematical models—using the biological effective dose concept and incorporating the RBEmax and RBEmin parameters (the limits of RBE at low and high dose, respectively—as shown in the Appendix). The RBE itself can then vary between these limits according to the dose per fraction used. These approaches provide useful insights into the problems that can occur in proton and ion beam therapy and how they may be optimised. This is because neutron ionisations in living tissues are mainly caused by recoil protons of energy proportional to the neutron energy: these are close to the proton energies that occur close to the Bragg peak region. To some extent, neutron RBE studies contain the highest RBE ranges found within proton and ion beams near Bragg peaks. In retrospect, neutrons were a useful radiobiological tool that has continued to inform the scientific and clinical community about the essential radiobiological principles of all forms of high linear energy transfer therapy. Neutron radiobiology and its implications should be taught on training courses and studied closely by clinicians, physicists, and biologists engaged in particle beam therapies.

Ion Beam Stimulation Therapy With a Nanoradiator as a Site-Specific Prodrug

Because Bragg-peak energy cannot be delivered individually to multiple scattered tumor infiltration or diffusive lesions, instead, energy of ion beam can be adjusted to traverse entire body for selective activation of the nanoparticles inside target lesions with the ion fluence comparable to Bragg peak. This Coulomb stimulation on nanoparticles generate low energy electrons (LEEs) and characteristic fluorescent X-ray (XFL) from the nanoparticle surface that effectively transform inert nanoparticles into a nanoradiator like conversion of prodrug into drug. In contrast, relatively small plateau dose absorbed on beam path ensure minimal effect on normal. This simple but innovative approach enable traversing ion beam therapy (TIBS) on either tumor infiltration or diffusive non-oncological lesions unprecedentedly. Theoretical background and unique efficacy of TIBS are demonstrated by several proof-of-concept studies with animal disease models and molecular-targeted high-Z NP.

High-dose carbon-ion based radiotherapy of primary and recurrent sacrococcygeal chordomas: long-term clinical results of a single particle therapy center

BackgroundThis study aimed to analyze the oncological long-term results and late toxicity of carbon ion-based radiotherapy (RT) of patients with sacral chordoma and to identify potential prognostic factors for local control (LC) and overall survival (OS).MethodsA total of 68 patients with sacral chordoma treated at the Heidelberg Ion Beam Therapy Center were included in this study. Of these 52 patients (77%) received a primary RT and 16 patients (23%) received a RT in a recurrent situation. All patients were treated with carbon ion RT (CIRT), either in combination with photons (n = 22; 32%) or as a monotherapy (n = 46; 68%), with a median radiation dose of 66 Gy RBE (range 60–74 Gy). In 40 patients (59%), RT was performed in the postoperative situation. Postoperative care included regular MRI scans. Local progression was defined as an enlargement of the maximum tumor diameter by 10% or a new tumor growth within the planning target volume (PTV). LC and OS were determined using the Kaplan-Meier method. Furthermore, the relevance of various prognostic factors for LC and OS was assessed by univariate and multivariate analysis.ResultsThe median follow-up period was 60 months (range 1.3–97.4 months). The 5-year rates for LC, progression-free survival, metastasis-free survival and OS were 53, 53, 52 and 74%, respectively. Local recurrence was observed in 31 patients (46%), occurring after a median follow-up time of 25 months (range 2.5–73.1 months). Only 10% of local recurrences occurred later than 5 years after RT. Statistical analysis showed that RT in the relapse situation corresponded to inferior LC rates compared to the primary situation, while other factors such as the GTV, radiation dose (EQD2) and treatment approach (CIRT alone vs. CIRT combined with photons) were insignificant. For OS after RT, patient age and PTV size proved to be significant predictors.The incidence of late toxicity ≥ III° according to CTCAE v5.0 was 21%. Sacral insufficiency fractures occurred in 49% of patients (maximum III°: 16%) and were thus by far the most frequent late side effect in our analysis. Radiogenic damage to the peripheral nerves, intestinal tract and skin was observed in only 9% (≥ III°: 5%), 3% (all II°) and 9% (all I°) of patients.ConclusionOur analysis showed only moderate long-term LC rates after carbon ion-based RT, with sacral chordomas having a particularly poor prognosis in the recurrent situation. Therefore, future studies should evaluate the safety and effectiveness of further dose escalation and hypofractionation of RT in sacral chordoma and weight potential benefits of dose escalation against side effects.

Characterizing Radiation Effectiveness in Ion Beam Therapy Part I: Introduction and Biophysical Modeling of RBE Using the LEMIV

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the inverted dose profile with a Bragg peak and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of the relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modelling of RBE and the microdosimetric measurements in complex radiation fields. This first paper gives a brief introduction into these fields and then focuses on aspects of biophysical modelling of RBE, specifically on semi-empirical approaches that are currently used in treatment planning for ion beam therapy. It summarizes the status and recent developments of the Local Effect Model (LEM) and its conceptual framework and shows examples of model validation using recent experimental data. The model is compared to other approaches, e.g. to the Microdosimetric-Kinetic Model (MKM), that builds the bridge to the experimental microdosimetric work.

Robust radiobiological optimization of ion beam therapy utilizing Monte Carlo and microdosimetric kinetic model

To develop a Monte Carlo (MC)-based and robust ion beam therapy optimization system that separates the optimization algorithm from the relative biological effectiveness (RBE) modeling. Robustly optimized dose distributions were calculated and compared across three ion therapy beams (proton, helium, carbon). The effect of different averaging techniques in calculating RBE in mixed beams was also investigated. Ion particles were transported in TOPAS MC. The microdosimetric-kinetic model (MKM) parameter, saturation corrected specific energy (), was calculated with a customized MKM implementation in TOPAS MC. Intensity modulated ion therapy robust optimization was performed by a quasi-Newton iterative method based on dose-volume objective function. The robust optimization took setup and range uncertainties into account. In the present work, the biological dose for each individual spot was calculated, and then summed together to calculate total biological dose. In other published works, radiosensitive parameters, such as , were first averaged over all beam spots within a mixed-beam field, after which biological dose was calculated using the averaged radiosensitive parameters. The difference between the two mixed-beam biological dose calculations was quantified. Robust plans were achieved with the three particle types. The effect of averaging depended on particle type. The difference between biological doses calculated with individual and averaged may be greater than 3% for a carbon beam. MC based radiobiological and robust optimization was made flexible to incorporate dose-volume histogram constraints and to be independent of RBE models. Iterative optimization with RBE models was feasible. Evaluation of the RBE calculation for mixed beam could be necessary if better accuracy was demanded.

Experimental comparison of clinically used ion beams for imaging applications using a range telescope

In particle therapy, the x-ray based treatment planning converting photon attenuation values to relative stopping power ratio (RSP) introduces clinically relevant range uncertainties. Recently, novel imaging technologies using transmission ion beams have been investigated to directly assess the water equivalent thickness (WET) of tissue, showing improved accuracy in RSP reconstruction, while potentially reducing the imaging dose. Due to their greater availability, protons have been mostly used for ion imaging. To this end, in this work, the influence of three ion species (protons, helium and carbon ions) on the image quality of radiographic WET retrieval has been explored with a dedicated experimental setup and compared to Monte Carlo (MC) simulations. Three phantom setups with different tissue interfaces and features have been irradiated with clinically validated proton, helium and carbon ion pencil beams under comparable imaging dose and beam settings at the Heidelberg Ion-Beam Therapy Center. Ion radiographies (iRADs) were acquired with an integration mode detector, that functions as a range telescope with 61 parallel plate ionization chambers. For comparison, experiments were reproduced in-silico with FLUKA MC simulations. Carbon ions provide iRADs with highest image quality in terms of normalized root mean square error, followed by helium ions and protons. All ions show similar capabilities of resolving WET for the considered phantoms, as shown by the similar average relative error < 3%. Besides for the slab phantom, MC simulations yielded better results than the experiment, indicating potential improvement of the experimental setup. Our results showed that the ability to resolve the WET is similar for all particles, intrinsically limited by the granularity of the detector system. While carbon ions are best suited for acquiring iRADs with the investigated integration mode detector, helium ions are put forward as a less technical challenging alternative.

Imaging with protons at MedAustron

Ion beam therapy has become a frequently applied form of cancer therapy over the last years. The advantage of ion beam therapy over conventional radiotherapy using photons is the strongly localized dose deposition, leading to a reduction of dose applied to surrounding healthy tissue. Currently, treatment planning for proton therapy is based on X-ray computed tomography, which entails certain sources of inaccuracy in calculation of the stopping power (SP). A more precise method to acquire the SP is to directly use high energy protons (or other ions such as carbon) and perform proton computed tomography (pCT). With this method, the ions are tracked prior to entering and after leaving the patient and finally their residual energy is measured at the very end. Therefore, an ion imaging demonstrator, comprising a tracking telescope made from double-sided silicon strip detectors and a range telescope as a residual energy detector, was set up. First measurements with this setup were performed at beam tests at MedAustron, a center for ion therapy and research in Wiener Neustadt, Austria. The facility provides three rooms for cancer treatment with proton beams as well as one which is dedicated to non-clinical research.This contribution describes the principle of ion imaging with proton beams in general as well as the design of the experimental setup. Moreover, first results from simulations and recent beam tests as well as ideas for future developments will be presented.

The societal impact of ion beam therapy

Ion beam therapy should be "democratized" through model-based patient selection, innovative technologies for better and faster treatment delivery, and substantial size and cost reduction. The disability-adjusted life year (DALY) concept can be used to quantify the societal benefit.

Secondary Malignancy Risk Following Proton vs. X-ray Treatment of Mediastinal Malignant Lymphoma: A Comparative Modeling Study of Thoracic Organ-Specific Cancer Risk.

Purpose: Proton radiotherapy (PRT) is potentially associated with a lower risk for secondary malignancies due to a decreased integral dose to the surrounding organs at risk (OARs). Prospective trials confirming this are lacking due to the need for long-term follow-up and the ethical complexities of randomizing patients between modalities. The objective of the current study is to calculate the risk for secondary malignancies following PRT and photon-based intensity-modulated radiotherapy (IMRT).Materials and Methods: Twenty-three patients (16 female and seven male), previously treated with active scanning PRT for malignant mediastinal lymphoma at Heidelberg Ion Beam Therapy Center, were retrospectively re-planned using helical photon IMRT. The risk for radiation-induced secondary malignancies was estimated and evaluated using two distinct prediction models (1–4).Results: According to the Dasu model, the median absolute total risk for tumor induction following IMRT was 4.4% (range, 3.3–5.8%), 9.9% (range, 2.0–27.6%), and 1.0% (range, 0.5–1.5%) for lung, breast, and esophageal cancer, respectively. For PRT, it was significantly lower for the aforementioned organs at 1.6% (range, 0.7–2.1%), 4.5% (range, 0.0–15.5), and 0.8% (range, 0.0–1.6%), respectively (p ≤ 0.01). The mortality risk from secondary malignancies was also significantly reduced for PRT relative to IMRT at 1.1 vs. 3.1% (p ≤ 0.001), 0.9 vs. 1.9% (p ≤ 0.001), and 0.7 vs. 1.0% (p ≤ 0.001) for lung, breast, and esophageal tumors, respectively. Using the Schneider model, a significant risk reduction of 54.4% (range, 32.2–84.0%), 56.4% (range, 16.0–99.4%), and 24.4% (range, 0.0–99.0%) was seen for secondary lung, breast, and esophageal malignancies, favoring PRT vs. X-ray-based IMRT (p ≤ 0.01).Conclusion: Based on the two prediction models, PRT for malignant mediastinal lymphoma is expected to reduce the risk for radiation-induced secondary malignancies compared with the X-ray-based IMRT. The young age and the long natural history of patients diagnosed with mediastinal lymphoma predisposes them to a high risk of secondary malignancies following curative radiotherapy treatment and, as a consequence, potentially reducing this risk by utilizing advanced radiation therapy techniques such as PRT should be considered.