Particle Therapy Research Articles

Carbon ion mono-energetic and spread-out Bragg peak measurements using nanocomposite Fricke gel dosimeters with LET-independent response

This study investigates the LET-dependence of dose measurements performed with a nanocomposite Fricke gel (NC-FG) upon irradiation with carbon ion beams to address the problem of quenching of gel dosimeters in high-LET particle therapy. The preparation of the NC-FG in a simple gel preparation device was performed for atmospheric and anoxic environmental conditions and two different container materials. Irradiation was performed with carbon ion beams at energies of 133.39MeV/u or 194.87MeV/u, complemented by a modulated 10 mm carbon ion spread-out Bragg peak (SOBP) irradiation. The R1 profiles obtained from the MRI readout were compared to the treatment planning system and a 2D-ionisation chamber array measurement performed for the mono-energetic and SOBP irradiations, respectively. For different dose levels, no difference in the gel response was obtained for the 3D-printed plastic containers, while the glass vials exhibited a linear dose response. Additional use of the glove box changes produced similar results. For both the mono-energetic and the SOBP irradiation, a linear dose response without quenching was observed. For depths ranging up to the Bragg peak position, the mono-energetic profiles deviated by less than ±15% from the planned dose distribution, excluding the lowest entrance surface dose (ESD). For the SOBP profiles, the deviation from the measured dose distribution was less than ±10% for depths between 20 mm and 33 mm. This study presents a LET-independent measurement of mono-energetic carbon ion Bragg peaks and, for the first time, a LET-independent measurement of a carbon ion SOBP with the NC-FG prepared in a simple gel preparation device under atmospheric conditions. The NC-FG provides a possible solution for 3D dosimetry in carbon ion radiotherapy.

3353: Image-guided particle therapy: Did we close the gap?

3353: Image-guided particle therapy: Did we close the gap?

Irradiation with Carbon Ions Effectively Counteracts Hypoxia-related Radioresistance in a Rat Prostate Carcinoma

Hypoxia in tumors is associated with increased malignancy and resistance to conventional photon radiation therapy. This study investigated the potential of particle therapy to counteract radioresistance in syngeneic rat prostate carcinoma. Subcutaneously transplanted R3327-HI tumors were irradiated with photons or carbon ions under acute hypoxic conditions, induced by clamping the tumor-supplying artery 10 min before and during irradiation. Dose-response curves were determined for the endpoint "local tumor control within 300 days" and compared with previously published data acquired under oxic conditions. Doses at 50% tumor control probability (TCD50) were used to quantify hypoxia-induced radioresistance relative to that under oxic conditions and also to quantify the increased effectiveness of carbon ions under oxic and hypoxic conditions relative to photons. Compared with those under oxic conditions, TCD50 values under hypoxic conditions increased by a factor of 1.53 ± 0.08 for photons and by a factor of 1.28 ± 0.06 for carbon ions (oxygen enhancement ratio). Compared with those for photons, TCD50 values for carbon ions decreased by a factor of 2.08 ± 0.13 under oxic conditions and by a factor of 2.49 ± 0.08 under hypoxic conditions (relative biological effectiveness). While the slope of the photon dose-response curves increased when changing from oxic to hypoxic conditions, the slopes were steeper and remained unchanged for carbon ions. The reduced oxygen enhancement ratio of carbon ions indicated that the required dose increase in hypoxic tumors was 17% lower for carbon ions than for photons. Additionally, carbon ions reduced the effect of intertumor heterogeneity on the radiation response. Therefore, carbon ions may confer a significant advantage for the treatment of hypoxic tumors that are highly resistant to conventional photon radiation therapy.

3225: Commissioning of the Fricke solution dosimeter for particle therapy

3225: Commissioning of the Fricke solution dosimeter for particle therapy

Current Status and Future Prospects of Particle Therapy for Hepatocellular Carcinoma

Current Status and Future Prospects of Particle Therapy for Hepatocellular Carcinoma

95: Phase Ib trial of Durvalumab plus tremelimumab with particle therapy for advanced HCC: DEPARTURE

95: Phase Ib trial of Durvalumab plus tremelimumab with particle therapy for advanced HCC: DEPARTURE

Tissue equivalent conversion of silicon-based microdosemeters in hadron therapy.

Silicon has been developed as a microdosemeter, as it can provide sensitive volumes at submicrometric levels, does not need a gas supply, has a fast response, and has low power consumption. However, since the energy response in silicon is not the same as that in tissue, a spectral conversion from silicon to tissue is necessary to obtain the probability distribution of energy deposition in tissue. In this work, we present a method for microdosimetric spectra conversion from silicon to tissue based on the scaled Fourier transformation and the geometric scaling factor, which shows relatively good results in the spectral conversion from diamond to tissue. The results illustrate that the method can convert the energy deposition spectra from silicon to tissue with proper accuracy. Meanwhile, the inconsistency between the converted and actual spectra due to the inherent difference was also observed. Whereas, the reasons for the disagreement are different. For the plateau part of the Bragg curve, the discrepancy between the converted and actual spectra is due to the poor tissue equivalent of silicon. For the proximal part of the Bragg curve, the spectral difference is attributed to the different shapes of the energy deposition spectra obtained in silicon and water, which is the same as that in the diamond. In summary, this method can be employed in the tissue equivalent conversion of silicon microdosemeter, but the poor tissue equivalent of silicon limited the accuracy of this method. In addition, the correction for the deviation between the converted and calculated spectra due to the difference in spectral shapes is required to improve the practicality of this mod.

An essentially radiation-transparent body coil integrated with a patient rotation system for MR-guided particle therapy.

The pursuit of adaptive radiotherapy using MR imaging for better precision in patient positioning puts stringent demands on the hardware components of the MR scanner. Particularly in particle therapy, the dose distribution and thus the efficacy of the treatment is susceptible to beam attenuation from interfering materials in the irradiation path. This severely limits the usefulness of conventional imaging coils, which contain highly attenuating parts such as capacitors and preamplifiers in an unknown position, and requires development of a dedicated radiofrequency (RF) coil with close consideration of the materials and components used. In MR-guided radiation therapy in the human torso, imaging coils with a large FOV and homogeneous B1 field distribution are required for reliable tissue classification. In this work, an imaging coil for MR-guided particle therapy was developed with minimal ion attenuation while maintaining flexibility in treatment. A birdcage coil consisting of nearly radiation-transparent materials was designed and constructed for a closed-bore 1.5 T MR system. Additionally, the coil was mounted on a rotatable patient capsule for flexible positioning of the patient relative to the beam. The ion attenuation of the RF coil was investigated in theory and via measurements of the Bragg peak position. To characterize the imaging quality of the RF coil, transmit and receive field distributions were simulated and measured inside a homogeneous tissue-simulating phantom for various rotation angles of the patient capsule ranging from 0° to 345° in steps of 15°. Furthermore, simulations with a heterogeneous human voxel model were performed to better estimate the effect of real patient loading, and the RF coil was compared to the internal body coil in terms of SNR for a full rotation of the patient capsule. The RF coil (total water equivalent thickness (WET) ≈ 420µm, WET of conductor ≈ 210µm) can be considered to be radiation-transparent, and a measured transmit power efficiency (B1 +/ ) between 0.17 µT/ and 0.26 µT/ could be achieved in a volume (Δz=216mm, complete x and y range) for the 24 investigated rotation angles of the patient capsule. Furthermore, homogeneous transmit and receive field distributions were measured and simulated in the transverse, coronal and sagittal planes in a homogeneous phantom and a human voxel model. In addition, the SNR of the radiation-transparent RF coil varied between 103 and 150, in the volume (Δz=216mm) of a homogeneous phantom and surpasses the SNR of the internal body coil for all rotation angles of the patient capsule. A radiation-transparent RF coil was developed and built that enables flexible patient to beam positioning via full rotation capability of the RF coil and patient relative to the beam, with results providing promising potential for adaptive MR-guided particle therapy.

The first real-world study on the role of carbon ion radiotherapy for oligo-metastatic, persistent, or recurrent (MPR) ovarian/fallopian tube cancer

IntroductionIn the multidisciplinary management of oligometastatic, persistent, or recurrent (MPR) ovarian cancer, radiotherapy (RT) is becoming a more and more worthwhile treatment to potentially improve the chronicity of the disease. Particle beam RT has proved to be effective in several gynecological malignancies, but so far no data are available for ovarian cancer. Material and MethodsThis is a real-world, retrospective, bi-institutional, single-arm study aimed to assess the effectiveness and the safety of carbon ion RT (CIRT) in this setting. The co-first endpoints are 1-year and 2-year actuarial local control (LC) rates and the objective response rate (ORR) defined on a “per lesion” basis. The secondary endpoint was toxicity. Actuarial outcomes were evaluated using the Kaplan-Meier method while potential predictors were explored using the Log-rank test. Bi-variable logistic regression was employed in the analysis of factors predicting the complete response on a per-lesion basis. Results26 patients accounting for a total of 36 lesions underwent CIRT with a total median dose of 52.8 Gy[RBE] (range: 39–64 Gy[RBE]). Five patients received CIRT for re-irradiation. No concomitant systemic therapies were administered during CIRT. Within 12 months after the treatment, 17 lesions (47 %) achieved complete response while 18 (50 %) obtained a partial response with an ORR of 97 %. The achievement of a complete response is related to the dose per fraction (>4.2 Gy[RBE], p = 0.04) and total dose (>52,8 Gy[RBE], p = 0.05). The 1-year LC was 92 % and the 2-year LC was 83 %, according to the achievement of a CR (p = 0.007) and GTV ≤ 14 cm3 (p = 0.024). No grade > 3 toxicities were recorded both in naïve and re-irradiated patients. PARP-i and anti-VEGF seemed not to exacerbate the risk of severe toxicities. ConclusionsCIRT was effective and safe in MPR ovarian cancers, even in the case of re-irradiation. Largest cohort studies and longer follow-up are needed to confirm these data.

The clinical roadmap in a dual-beam hadrontherapy centre: tumour-based and patient-tailored selection criteria, management of range uncertainties and oncological patient pathway

PurposeIn the present short report, we encompass the radiobiological and dosimetric advantages of particle beam radiotherapy and we illustrate the oncological pathway for patients eligible for hadrontherapy being used at the National Center for Oncological Hadrontherapy (CNAO).MethodsWith a narrative approach, we examined the clinical and practical aspects of hadrontherapy compared to traditional photon beam radiotherapy. We described the need to select patients considering the intrinsic characteristics both of the tumour and the patient. Moreover, we described the decisional oncological tree and the patient pathway by our facility.ResultsConsidering the dosimetric and radiobiological characteristics of particle beam radiotherapy, the selection of patients can not be done regardless of the intrinsic tumour and patient hallmarks. In particular, the tumour radioresistance, the patient radiosensitivity and the need to avoid post-actinic toxicities in long-term survivors should guide the clinical indication. The finite range of particles should be considered to avoid treatment uncertainties. Multidisciplinary national and international collaboration is crucial to better manage patients to treat with hadrontherapy and to create robust clinical evidence.ConclusionHadrontherapy, with its distinctive physical and biological advantages, heralds a promising era in the field of precision radiotherapy. Patients’ radiosensitivity, tumour radioresistance, and treatment uncertainties should be considered to enhance the efficacy and to ameliorate the selection of patients.

Current status and future trends in particle therapy – lessons from an interdisciplinary workshop

PurposeTo provide an introduction to the special issue containing the proceedings of the workshop on cancer therapy using hadrons (proton, carbon ions or boron neutron capture therapy) that was held in Pavia in October 2023 and organized by CNAO and IAEA.MethodsPapers contained in the issue are briefly summarized.ResultsThis issue contains a collection of papers from the workshop that provide a great opportunity to learn about the status and progress of this technology.ConclusionsParticle therapy is exponentially growing worldwide. While several clinical trials are now providing convincing evidence of the effectiveness of the treatment in tumor control and reduced toxicity, the technology remains expensive and the cost effectiveness is still under debate. The IAEA-CNAO workshop provided a clear picture of the state of the art and future prospective of this technology.

Radiolysis of myoglobin concentrated gels by protons: specific changes in secondary structure and production of carbon monoxide

While particle therapy has been used for decades for cancer treatment, there is still a lack of information on the molecular mechanisms of biomolecules radiolysis by accelerated ions. Here, we examine the effects of accelerated protons on highly concentrated native myoglobin, by means of Fourier transform infrared and UV–Visible spectroscopies. Upon irradiation, the secondary structure of the protein is drastically modified, from mostly alpha helices conformation to mostly beta elements at highest fluence. These changes are accompanied by significant production of carbon monoxide, which was shown to come from heme degradation under irradiation. The radiolytic yields of formation of denatured protein, carbon monoxide, and of heme degradation were determined, and found very close to each other: G+denatured Mb ≈ G+CO ≈ G-heme = 1.6 × 10–8 ± 0.1 × 10–8 mol/J = 0.16 ± 0.01 species/100 eV. The denaturation of the protein to a beta structure and the production of carbon monoxide under ion irradiation are phenomena that may play an important role in the biological effects of ionizing radiation.

Particle Therapy for Cancer of the Head & Neck and Tracheoesophageal Region：Current Status and Future Prospects

Particle Therapy for Cancer of the Head & Neck and Tracheoesophageal Region：Current Status and Future Prospects

Impact of proton PBS machine operating parameters on the effectiveness of layer rescanning for interplay effect mitigation in lung SBRT treatment.

Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

The MedAustron particle therapy accelerator facility

The MedAustron particle therapy accelerator facility

Comparing efficacy of charged-particle therapy with brachytherapy in treatment of uveal melanoma.

Uveal melanoma (UM) is the most common primary ocular tumour in adults. The most used eye-preserving treatments are charged-particle therapy (CPT) and brachytherapy. We performed a systematic review and meta-analysis to compare efficacies and complications of these two radiotherapies. We searched EMBASE, PubMed, MEDLINE, and the Cochrane Library from January 2012 to December 2022. Two independent reviewers identified controlled studies comparing outcomes of CPT versus brachytherapy. Case series that utilize either treatment modality were also reviewed. One hundred fifty studies met the eligibility criteria, including 2 randomized control trials, 5 controlled cohort studies, and 143 case series studies. We found significant reduction in local recurrence rate among patients treated with CPT compared to brachytherapy (Odds ratio[OR] 0.38, 95% Confidence interval [CI] 0.24-0.60, p < 0.01). Analysis also showed a trend of increased risks of secondary glaucoma after CPT. No statistically significant differences were found in analyzing risks of mortality, enucleation, and cataract. Our study suggested no difference in mortality, enucleation rate and cataract formation rate comparing the two treatments. Lower local recurrence rate and possibly higher secondary glaucoma incidence was noted among patients treated with CPT. Nevertheless, the overall level of evidence is limited, and further high-quality studies are necessary to provide a more definitive conclusion.

Data Processing Engine (DPE): data analysis tool for particle tracking and mixed radiation field characterization with pixel detectors Timepix

Hybrid semiconductor pixelated detectors from the Timepix family are advanced detectors for online particle tracking, offering energy measurement and precise time stamping capabilities for particles of various types and energies. This inherent capability makes them highly suitable for various applications, including imaging, medical fields such as radiotherapy and particle therapy, space-based applications aboard satellites and the International Space Station, and industrial applications. The data generated by these detectors is complex, necessitating the development and deployment of various analytical techniques to extract essential information.For this purpose, and to aid the Timepix user community, it was designed and developed the“Data Processing Engine” (DPE) as an advanced tool for data processing designed explicitly for Timepix detectors. The functionality of the DPE is structured into three distinct processing levels: i) Pre-processing: this phase involves clusterization and the application of necessary calibrations and corrections. ii) Processing: this stage includes particle classification, employing machine learning algorithms, and the recognition of radiation fields. iii) Post-processing: involves various analyses, such as directional analysis, coincidence analysis, frame analysis, Compton directional analysis, and the generation of physics products, are performed. The core of the DPE is supported by an extensive experimental database containing calibrations and referential radiation fields of typical environments, including protons, ions, electrons, gamma rays and X rays, as well as thermal and fast neutrons. To enhance accessibility, the DPE is implemented into various user interface platforms such as a command-line tool, an application programming interface, and as a graphical user interface in the form of a web portal. The DPE's broad utility is exemplified through its integration into various applications and developments.

Comprehensive beam delivery latency evaluation for gated proton therapy system using customized multi-channel signal acquisition platform.

Beam delivery latency in respiratory-gated particle therapy systems is a crucial issue to dose delivery accuracy. The aim of this study is to develop a multi-channel signal acquisition platform for investigating gating latencies occurring within RPM respiratory gating system (Varian, USA) and ProBeam proton treatment system (Varian, USA) individually. The multi-channel signal acquisition platform consisted of several electronic components, including a string position sensor for target motion detection, a photodiode for proton beam sensing, an interfacing board for accessing the trigger signal between the respiratory gating system and the proton treatment system, a signal acquisition device for sampling and synchronizing signals from the aforementioned components, and a laptop for controlling the signal acquisition device and data storage. RPM system latencies were determined by comparing the expected gating phases extracted from the motion signal with the trigger signal's state turning points. ProBeam system latencies were assessed by comparing the state turning points of the trigger signal with the beam signal. The total beam delivery latencies were calculated as the sum of delays in the respiratory gating system and the cyclotron proton treatment system. During latency measurements, simulated sinusoidal motion were applied at different amplitudes and periods for complete beam delivery latency evaluation under different breathing patterns. Each breathing pattern was repeated 30 times for statistical analysis. The measured gating ON/OFF latencies in the RPM system were found to be 104.20±13.64ms and 113.60±14.98ms, respectively. The measured gating ON/OFF delays in the ProBeam system were 108.29±0.85ms and 1.20±0.04ms, respectively. The total beam ON/OFF latencies were determined to be 212.50±13.64ms and 114.80±14.98ms. With the developed multi-channel signal acquisition platform, it was able to investigate the gating lags happened in both the respiratory gating system and the proton treatment system. The resolution of the platform is enough to distinguish the delays at the millisecond time level. Both the respiratory gating system and the proton treatment system made contributions to gating latency. Both systems contributed nearly equally to the total beam ON latency, with approximately 100ms. In contrast, the respiratory gating system was the dominant contributor to the total beam OFF latency.

Innovative approaches to enhance high-LETd tumor targeting in carbon ion radiotherapy

PurposeTo present novel approaches in particle therapy that could result in an improvement of patient outcome.MethodsTechnological/planning and biological innovations could bring particle therapy into a new area of precision medicine. However, several hurdles have to be overcome in order to transform these R&D opportunities into clinical advantages. In this contribution, we summarize the potential advantages of novel tumor targeting, through high-LETd boosting strategies with carbon ions, over standard IMPT: LETd-optimization for IMPT plan, IMPTLET, and spot-scanning hadron arc (SHArc) therapy. Two patient cases are presented to showcase the benefit: a pancreatic cancer patient (PATA) and a recurrent glioblastoma patient (PATB).ResultsFor both patients, the prescription dose and target/organs at risk (OARs) optimization goals were reached for the three techniques. In standard IMPT, the maximum LETd is placed outside of the target volume and extends into normal tissues. For the gross target volume (GTV), mean LETd values were, on average, around ∼40–60 keV/µm. IMPTLET allowed an increase in the GTV minimum LETd from 38.4 keV/µm to 48.6 keV/µm, and from 55.1 to 87.1 keV/µm, for PATA and PATB, respectively. SHArc led to an enhancement of the maximum LETd in the GTV up to at least 125 keV/µm, while the minimum GTV LETd were 47.2 keV/µm and 46.1 keV/µm, respectively. For PATA, SHArc lowers the maximum LETd in the gastrointestinal tract to 47.5 keV/µm compared to 88.0 keV/µm and 83.0 keV/µm found for the IMPT and IMPTLET plans, respectively.ConclusionsMany technological and biological innovations could enhance our current clinical approach. Following the current success of the IMPTLET introduction in clinic, SHARc will represent an interesting clinical option in carbon ion therapy.

Monitoring of carbon ion therapeutic beams with thin silicon sensors

Single ion counting in particle therapy may lead to new beam monitoring systems, enabling innovative delivery strategies that are faster and more sensitive than those currently used in clinics. Previous studies carried out by the University and the National Institute of Nuclear Physics (INFN) of Turin have demonstrated the feasibility of using thin silicon detectors to count single protons in clinical beams. The aim of this work is to report the performance of a strip-segmented 60-μm thick silicon PIN sensor used for single carbon ion discrimination. All measurements were performed using the CNAO synchrotron at different beam energies covering the clinical energy range (115–399 MeV/u). Signals from the sensor strips were read using a custom amplifier board and sampled with a 5 GS/s digitizer. The carbon ion signals were analyzed in terms of amplitude, duration, and deposited charge at different sensor bias voltages.