Carbon Ion Beams Research Articles

2239: Monte Carlo calculations of beam quality correction factors for monoenergetic carbon-ion beams

2239: Monte Carlo calculations of beam quality correction factors for monoenergetic carbon-ion beams

Optically stimulated luminescence detectors for LET determination and dosimetry in ion beam therapy

Optically stimulated luminescence detectors (OSLDs) have been utilized for various dosimetry applications for many years. The use of Al2O3:C OSLDs for proton dosimetry began over a decade ago, taking advantage of the correlation between the ionization density of the radiation field and the ratio of intensities of the material’s two emission bands. The correlation allows for determining both linear energy transfer (LET) and dose in proton beams, with corrections for ionization quenching derived from the LET. However, the previous methodology for proton dosimetry and simultaneous LET determination with Al2O3:C OSLDs was cumbersome and occasionally associated with large uncertainties, while carbon beam dosimetry posed further challenges due to an elevated LET.This paper reviews the recent advancements in ion beam dosimetry and LET determination using OSLDs. Employing Al2O3:C,Mg OSLDs alongside improved, automatized read-out techniques, and the use of other radiation quality metrics than averaged LET, has removed most of the previous obstacles for ion beam dosimetry with OSLDs.The feasibility of simultaneous LET determination and dosimetry in ion beams is demonstrated through two case studies involving realistic proton and carbon ion therapy scenarios.

The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy.

Given that the original tumor microenvironment of oral cancer cannot be reproduced, predicting the therapeutic effects of irradiation using monolayer cultures and animal models of ectopic tumors is challenging. Unique properties of carbon-ion irradiation (CIR) characterized by the Bragg peak exert therapeutic effects on tumors and prevent adverse events in surrounding normal tissues. However, the underlying mechanism remains unclear. The biological effects of CIR were evaluated on three-dimensional (3D) in vitro models of normal oral mucosa (NOMM) and oral cancer (OCM3 and OCM4) consisting of HSC-3 and HSC-4 cells. A single 10- or 20-Gy dose of CIR was delivered to NOMM, OCM3, and OCM4 models. Histopathological and histomorphometric analyses and labeling indices for Ki-67, γH2AX, and TUNEL were examined after CIR. The concentrations of high mobility group box 1 (HMGB1) were measured. NOMM exhibited epithelial thinning after CIR, which could be caused by the decreased presence of Ki-67-labeled basal cells. The relative proportion of the thickness of cancer cells to the underlying stroma in cancer models decreased after CIR. This finding appeared to be supported by changes in the three labeling indices, indicating CIR-induced cancer cell death, mostly via apoptosis. Furthermore, the three indices and the HMGB1 release levels significantly differed among the OCM4 that received different doses and with different incubation times after CIR while those of the OCM3 models did not, suggesting more radiosensitivity in the OCM4. The three 3D in vitro models can be a feasible and novel tool to elucidate radiation biology.

Development of a biocompatible radiotherapy spacer using 3D printing and microcellular foaming process for enhanced prostate cancer treatment

In this study, a new active spacer was developed using three-dimensional (3D) printing technology and microcellular foaming process to overcome the limitations of current spacers used in prostate cancer treatment. In prostate cancer treatment, a spacer is inserted between the prostate and rectum to increase the distance between the two organs so as to reduce the radiation dose to the rectum. Radiotherapy spacer is widely used in particle therapy, such as proton and carbon beams, and X-ray radiation therapies, including intensity-modulated radiotherapy and stereotactic body radiation therapy. However, existing spacers have been reported to cause significant side effects. Therefore, this study introduces a 3D printing technique using polycaprolactone to develop a spacer that provides customized treatment and minimizes side effects. This technique utilizes the volume expansion that occurs when a 3D spacer printed to fit a patient’s organs undergoes foaming through a supercritical carbon dioxide (scCO2)-assisted microcellular foaming process. Additionally, the use of scCO2 allows simultaneous gas absorption and sterilization, thereby reducing the number of process steps. This study confirms the potential of the newly developed spacer to provide effective and safe radiotherapy for prostate cancer, reduce patient discomfort, and minimize rectal side effects during radiation treatment.

Monte Carlo simulation of initial and volume ion recombination correction factor in plane parallel ionization chambers exposed to ion beams

Objective. Accurate reference dosimetry with ionization chambers (ICs) relies on correcting for various influencing factors, including ion recombination. Theoretical frameworks, such as the Boag and Jaffe theories, are conventionally used to describe the ion recombination correction factors. Experimental methods are time consuming, the applicability may be limited and, in some cases, impractical to be used in clinical routine. The development of simulation tools becomes necessary to enhance the understanding of recombination under circumstances that may differ from conventional use. Before progressing, it is crucial to benchmark novel approaches to calculate ion recombination losses under known conditions. In this study, we introduce and validate a versatile simulation tool based on a Monte Carlo scheme for calculating initial and volume ion recombination correction factors in air-filled ICs exposed to ion beams with clinical dose rates. Approach. The simulation includes gaussian distribution of ion positions to model the distribution of charge carriers along the chamber volume. It accounts for various physical transport effects, including drift, diffusion, space charge screening and free electron fraction. To compute ion recombination, a Monte Carlo scheme is used due to its versatility in multiple geometries, without exhibiting convergence problems associated with numerically solved procedures. Main results. The code is validated in conventional dose rates against Jaffe’s theory for initial recombination and Boag’s theory for volume recombination based on parameters derived from experimental data including proton, helium and carbon ion beams measured with a plane parallel IC. Significance. The simulation demonstrates excellent agreement, typically 0.05% or less relative difference with the theoretical and experimental data. The current code successfully predicts ion recombination correction factors, in a large variety of ion beams, including different temporal beam structures.

Carbon - 12C ion radiation-induced cell death and molecular mechanisms in malignant cells: Evidence from in vivo and in vitro

Conventional radiotherapy has been revolutionized for several decades. Recently, the delivery of high linear energy transfer (LET) radiation such as heavy carbon ion therapy has gained more attention. Among all low-energy therapies such as photon, X-ray, and gamma radiation therapy, 12C heavy carbon ion therapy is the best therapy for cancer treatment due to its high relative biological effectiveness (RBE). It has been studied that many tumors show resistance to chemotherapy and low energy transfer radiation. The unique nature of high LET shows unique Bragg peaks where very little radiation are applied on the tumor cells and better results can be achieved. It effectively kills the tumor cells without affecting the normal cells. There are some limitations to conventional radiotherapy. Radiotherapy with the low LET group may not work properly. Carbon ion radiation (CIR) induces malignant cell death in different modes, such as apoptosis, senescence, autophagy, immunogenic cell death and necrosis. Heavy carbon ion therapy enhances cell death by altering different molecular signalling pathways such as p53, AKT, MEK, caspase and STAT–3. Investigation of the major molecular cell death by carbon ion irradiation is very essential to understand the modalities of heavy carbon ion induced cell death. In this context, the investigation of different signaling cascades may open new horizons in cancer treatment. The therapeutic efficacy and application of heavy carbon ion beams along with some molecular inhibitors, radio sensitizers, and gene therapy would be helpful for future cancer treatment. Therefore, a more thorough investigation in this field is needed. The current review article highlights the recent advances in cancer therapy research based on Carbon 12C Ion radiation-induced cell death.

Dosimetric impact of stopping power for human bone porosity with dual-energy computed tomography in scanned carbon-ion therapy treatment planning

Few reports have documented how the accuracy of stopping power ratio (SPR) prediction for porous bone tissue affects the dose distribution of scanned carbon-ion beam therapy. The estimated SPR based on single-energy computed tomography (SECT) and dual-energy CT (DECT) were compared for the femur of a Rando phantom which simulates the porosity of human bone, NEOBONE which is the hydroxyapatite synthetic bone substitute, and soft tissue samples. Dose differences between SECT and DECT were evaluated for a scanned carbon-ion therapy treatment plan for the Rando phantom. The difference in the water equivalent length was measured to extract the SPR of the examined samples. The differences for SPR estimated from the DECT-SPR conversion were small with − 1.8% and − 3.3% for the Rando phantom femur and NEOBONE, respectively, whereas the differences for SECT-SPR were between 7.6 and 70.7%, illustrating a 1.5-mm shift of the range and a dose difference of 13.3% at maximum point in the evaluation of the dose distribution. This study demonstrated that the DECT-SPR conversion method better estimated the SPR of the porosity of bone tissues than SECT-SPR followed by the accurate range of the carbon-ion beams on carbon-ion dose calculations.

Relative Biological Effectiveness of Carbon Ion Beams for Induction of Medulloblastoma with Radiation-specific Chromosome 13 Deletion in Ptch1+/- Mice.

Carbon ion radiotherapy (CIRT) for pediatric cancer is currently limited because of the unknown risk of induction of secondary cancers. Medulloblastoma of Ptch1+/- mice offers a unique experimental system for radiation-induced carcinogenesis, in which tumors are classified into spontaneous and radiation-induced subtypes based on their features of loss of heterozygosity (LOH) that affect the wild-type Ptch1 allele. The present study aims to investigate in young Ptch1+/- mice the carcinogenic effect, and its age dependence, of the low-linear energy transfer (LET, ∼13 keV/µm) carbon ions, to which normal tissues in front of the tumor are exposed during therapy. We irradiated Ptch1+/- mice at postnatal day (P) 1, 4, or 10 with 290 MeV/u carbon ions (0.05-0.5 Gy; LET, 13 keV/µm) and monitored them for medulloblastoma development. Loss of heterozygosity of seven genetic markers on chromosome 13 (where Ptch1 resides) was studied to classify the tumors. Carbon ion exposure induced medulloblastoma most effectively at P1. The LOH patterns of tumors were either telomeric or interstitial, the latter occurring almost exclusively in the irradiated groups, allowing the use of interstitial LOH as a biomarker of radiation-induced tumors. Radiation-induced tumors developed during a narrow age window (most strongly at P1 and only moderately at P4, with suppressed tumorigenesis at P10). Calculated using previous results using 137Cs gamma rays, the values for relative biological effectiveness (RBE) regarding radiation-induced tumors were 4.1 (3.4, 4.8) and 4.3 (3.3, 5.2) (mean and 95% confidence interval) for exposure at P1 and 4, respectively. Thus, the RBE of carbon ions for medulloblastoma induction in Ptch1+/- mice was higher than the generally recognized RBE of 1-2 for cell killing, chromosome aberrations, and skin reactions.

Simulation and Measurement of Carbon Ion Beam Emittance in the Channel of Radiobiological Research at the Accelerator Complex U-70

The technique for determining the emittance of carbon ion beams by measuring their transverse dimensions at the end of the air gap of the channel is described. The inverse transformation of phase ellipses is considered, taking into account multiple Coulomb scattering of particles and the presence of dispersion in the carbon ion beam. The values of betatron emittance before the first quadrupole lens are given and compared with data obtained by direct calculation starting from the inner target. Inaccuracies in the calculated and measured emittance values are discussed. Simulations and measurements were performed at beam energies of 200, 300, and 400 MeV/nucleon in front of the target.

Measurements of the Neutron Field Parameters with Monitors based on the Gas-Filled Proportional Counters

Neutron monitors with the gas filled proportional counters inside and first data were presented at RuPAC-2018 and RuPAC-2021 conferences. It is planned to use such devices to monitor the stability of irradiation conditions during radiation therapy sessions. We present here the calibration procedure for these monitors at AmBe neutron source, and the new data. These monitors have been used to measure the neutron fluence behind the shielding of the 450 MeV/nucleon carbon beam based experimental facility “Shared use Center – radiobiological stand with the carbon beam of the U-70 accelerator at IHEP”. The measurements were supported by the set of extensive simulations using the CERN FLUKA code. Good agreement between the FLUKA simulations and measurements was shown. Even single monitor with lead insertion calibrated at AmBe neutron source allows to have a good result in the real neutron field. The possibility to estimate the fluence of the high energy neutrons with the energy above 10 MeV using data from the pair of monitors was demonstrated. To improve the quality of the measurements one needs to take into account difference between calibration and measurements conditions.

Carbon Ion Beam Radiation Therapy as Part of a Trimodal Therapy for Non-small Cell Superior Sulcus Tumors: The INKA Study

Purpose/ObjectiveSuperior sulcus tumors are frequently treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery in a trimodal approach. The INKA study evaluated the replacement of photon irradiation by carbon ion radiotherapy (C12-RT) in this regimen. Material/methodsThe prospective INKA-study included patients with locally advanced non-small cell superior sulcus tumors (<cN3 cM0). Patients received 2 cycles of cisplatin and vinorelbine as per local standard. During the second cycle, 39Gy(RBE) of hypofractionated C12-RT in 13 fractions were applied. Surgery following an FDG-PET/CT restaging was performed 2 weeks later. The primary endpoint was feasibility and safety measured by the incidence of CTCAE (v4.0) grade 3/4 toxicity and/or discontinuation due to any reason. Secondary endpoints included the morphological (RECIST 1.0), metabolic (PERCIST 1.0) and histopathological response after nCRT as well as Quality of Life measurement (QLQ-C30/LC13). ResultsBetween 2015 and 2020, 14 patients were included and received nCRT. No grade 3/4 toxicity occurred with no discontinuation due to toxicity. Before surgery, 8 patients (57%) showed a partial response on CT scan. Thirteen patients showed a metabolic response (mCR=1, mPR=12). Three patients were judged as inoperable after nCRT (21%). In patients with resection, a pathological CR was seen in 2 patients (19%) and near-complete remission (<10% vital tumor cells) in 6 patients (55%). Pain score was more than halved compared to baseline (mean: 69.2±26.2 vs. 30.6 ± 29.1; p=0.005) after completion of nCRT and before surgery. ConclusionThe INKA trial is the first study to evaluate nCRT with C12-RT and showed excellent response, low toxicity and rapid pain relief.

SiC and Si detectors comparison for high carbon energy spectrometry

An innovative SiC Schottky junction and a traditional p-n Si surface barrier detector have been compared to detect carbon ions with MeVs kinetic energy. To this, a comparison was performed during Rutherford backscattering spectrometry (RBS) using 2–10 MeV carbon ion beams. The energy resolution and detection efficiency for RBS analysis using the two detectors and their detection electronics are presented.The detector parameters dependencies on the surface passivating layers, ion energy and current dependence, ion penetration depth, detection efficiency, energy resolution, and others are discussed.The comparison of RBS analysis with SiC and Si is investigated highlighting the advantages and disadvantages of using SiC with respect to the traditional Si surface barrier detectors. The two detectors employed for proton, helium and carbon RBS spectrometry of different targets have been also compared on the base of the literature data.

Range Different of Mono-Energetic 290 MeV/u Carbon Ion Across Geant4 Version with Variation of I-values

The mean ionization potential (I-value) is a primary determinant of the position of the heavy ion Bragg peak. To minimize their impact on beam range errors and quantify their uncertainties, the currently used I-values in Geant4 material database are revisited. The study aims at comparing set of I-values in different Geant4 versions and cross validation with PHITS Monte Carlo (MC) code. The Bragg curves of mono-energetic 290 MeV/u carbon ion beams in a Polymethyl Methacrylate (PMMA) phantom were simulated using Geant4 versions 10.6.2 and 11.2.1. Similar beam energies were replicated using the PHITS code. The Bragg curves showed good agreement between the two versions of Geant4 MC code for an I-value of 74 eV, corresponding to G4_PLEXIGLASS in the material database. When the I-value was lowered to 65 eV and 48 eV, the Bragg curves from Geant4 version 11.2.1 shifted to shallower depths. This research provides insights for evaluating the Geant4 physics model.

Comparison of mutation spectra induced by gamma-rays and carbon ion beams.

The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and X-rays. This indicates a difference in the DNA damage produced by low and high LET radiations and their biological effects. We have been studying the differences in DNA damage produced by gamma-rays and carbon ion beams. Therefore, we analyze mutations induced by both ionizing radiations to discuss the differences in their biological effects in this study. pUC19 plasmid DNA was irradiated by carbon ion beams in the solution containing 1M dimethyl sulfoxide to mimic a cellular condition. The irradiated DNA was cloned in competent cells of Escherichia coli. The clones harboring some mutations in the region of lacZα were selected, and the sequence alterations were analyzed. A one-deletion mutation is significant in the carbon-irradiated DNA, and the C:G↔T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C↔T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations.

Hypofractionated proton and carbon ion beam radiotherapy for sacrococcygeal chordoma (ISAC): An open label, randomized, stratified, phase II trial

IntroductionSacrococcygeal chordomas have high recurrence rates and are challenging to treat. MethodsIn this phase II prospective, randomized, stratified trial, the safety and feasibility of hypofractionated ion radiation therapy were investigated. The primary focus was monitored through the incidence of Grade 3–5 NCI-CTC-AE toxicity. Secondary endpoints included local progression-free (LPFS) and overall survival (OS). ResultsThe study enrolled 82 patients with primary (87 %) and recurrent (13 %) inoperable or incompletely resected sacral chordomas from January 2013 to July 2022, divided equally into proton therapy (Arm A) and carbon ion beam therapy (Arm B) groups, each receiving a total dose of 64 Gy (RBE) in 16 fractions, 5–6 fractions per week. Overall 74 % of patients received no previous surgery and 66 % of tumors were confirmed by a brachyury staining. The mean and median Gross Tumor Volume at the time of treatment (GTV) was 407 ml and 185 ml, respectively. The median follow-up of the surviving patients was 44.7 months, and the 2-year and 4-year OS rates were 96 % and 81 %, respectively. Factors such as smaller GTV and younger age trended towards better OS. The LPFS after 2-year and 4-year was 84 % and 70 %, respectively. Male gender emerged as a significant predictor of LPFS. There was no significant difference between the treatment groups. We observed five grade 4 wound healing disorders (6 %). ConclusionThe initial response rates were promising; however local control was not sustained. More comparative research on fractionation schemes is essential to refine treatment approaches for inoperable sacral chordoma.

Diamond energy-dispersive dosimeter for measuring linear energy deposition distributions in clinical carbon beam therapy

A thin diamond membrane energy-dispersive dosimeter 50 μm thick was fabricated for estimating clinical dose distribution. In contrast to conventional semiconductors, diamond wide-bandgap semiconductors are expected to have excellent radiation tolerance and biological compatibility based on the linear relationship of stopping power ratio for clinical carbon particles. Linear energy transfer (LET) spectra were obtained along with the Bragg curve for a clinical carbon beam generated at Gunma University Heavy Ion Medical Center. The relative biological effectiveness (RBE) distributions were estimated from the LET spectra for both the mono-energy and spread-out Bragg peak irradiation configurations. The diamond detector was also used as a solid ionization chamber to obtain the radiation-induced current (RIC) distribution, which represents the physical dose distribution. The clinical dose distribution was estimated from the RIC and RBE distributions as proof of concept for the clinical carbon beam therapy field with a single-chip diamond energy-dispersive dosimeter.

Effect of 70MeV 12C5+ ion beam on structural and dielectric properties of PVC, PVDF, PVC-PVDF and PVC-PVDF-GO hybrid nanocomposites

The PVC-PVDF-GO nanocomposites thin films were prepared by solution casting method. A thin film of Polyvinyl chloride (PVC), Polyvinylidene fluoride (PVDF), PVC-PVDF-GO was uniformly irradiated with a carbon ion beam at 70 MeV over a surface of 1 cm2 in a vacuum of almost 5 × 10−7 torr with ion fluencies of 1 × 1012 and 2 × 1013 ions/cm2. Fourier transform infrared (FTIR) spectroscopy was observed to track changes in the β-content, represented as F(β)%, during the recrystallization of PVDF after irradiation. At ambient temperature, the variation of dielectric constant and dielectric loss has been studied for pristine and irradiated samples. Ion beam irradiation caused significant changes to the dielectric constant and dielectric loss. After irradiation, the dielectric constant (ϵ′) increases at lower fluence (1 × 1012 ions/cm2), but decreases at higher fluence (2 × 1013 ions/cm2) in comparison with the pristine polymer samples. In PVDF, free radicals are generated by chain scission and cross-linking.

Towards precise LET measurements based on energy deposition of therapeutic ions in Timepix3 detectors

Objective. There is an increasing interest in calculating and measuring linear energy transfer (LET) spectra in particle therapy in order to assess their impact in biological terms. As such, the accuracy of the particle fluence energy spectra becomes paramount. This study focuses on quantifying energy depositions of distinct proton, helium, carbon, and oxygen ion beams using a silicon pixel detector developed at CERN to determine LET spectra in silicon. Approach. While detection systems have been investigated in this pursuit, the scarcity of detectors capable of providing per-ion data with high spatial and temporal resolution remains an issue. This gap is where silicon pixel detector technology steps in, enabling online tracking of single-ion energy deposition. The used detector consisted of a 300 µm thick silicon sensor operated in partial depletion. Main results. During post-processing, artifacts in the acquired signals were identified and methods for their corrections were developed. Subsequently, a correlation between measured and Monte Carlo-based simulated energy deposition distributions was performed, relying on a two-step recalibration approach based on linear and saturating exponential models. Despite the observed saturation effects, deviations were confined below 7% across the entire investigated range of track-averaged LET values in silicon from 0.77 keV µm−1 to 93.16 keV µm−1. Significance. Simulated and measured mean energy depositions were found to be aligned within 7%, after applying artifact corrections. This extends the range of accessible LET spectra in silicon to clinically relevant values and validates the accuracy and reliability of the measurements. These findings pave the way towards LET-based dosimetry through an approach to translate these measurements to LET spectra in water. This will be addressed in a future study, extending functionality of treatment planning systems into clinical routine, with the potential of providing ion-beam therapy of utmost precision to cancer patients.

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry

Background and purposeTo investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. Materials and methodsThis multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. ResultsA total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7–49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %–85.5 %) and OS was 92.5 % (95 % CI: 89.3 %–95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. ConclusionsParticle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

The potential of mixed carbon–helium beams for online treatment verification: a simulation and treatment planning study

Objective. Recently, a new and promising approach for range verification was proposed. This method requires the use of two different ion species. Due to their equal magnetic rigidity, fully ionized carbon and helium ions can be simultaneously accelerated in accelerators like synchrotrons. At sufficiently high treatment energies, helium ions can exit the patient distally, reaching approximately three times the range of carbon ions at an equal energy per nucleon. Therefore, the proposal involves adding a small helium fluence to the carbon ion beam and utilizing helium as an online range probe during radiation therapy. This work aims to develop a software framework for treatment planning and motion verification in range-guided radiation therapy using mixed carbon–helium beams. Approach. The developed framework is based on the open-source treatment planning toolkit matRad. Dose distributions and helium radiographs were simulated using the open-source Monte Carlo package TOPAS. Beam delivery system parameters were obtained from the Heidelberg Ion Therapy Center, and imaging detectors along with reconstruction were facilitated by ProtonVDA. Methods for reconstructing the most likely patient positioning error scenarios and the motion phase of 4DCT are presented for prostate and lung cancer sites. Main results. The developed framework provides the capability to calculate and optimize treatment plans for mixed carbon–helium ion therapy. It can simulate the treatment process and generate helium radiographs for simulated patient geometry, including small beam views. Furthermore, motion reconstruction based on these radiographs seems possible with preliminary validation. Significance. The developed framework can be applied for further experimental work with the promising mixed carbon–helium ion implementation of range-guided radiotherapy. It offers opportunities for adaptation in particle therapy, improving dose accumulation, and enabling patient anatomy reconstruction during radiotherapy.