Feasibility of medical radioisotope production based on the proton beams at China Spallation Neutron Source

The utilization of a proton beam from the China Spallation Neutron Source(CSNS)for producing medical radioisotopes is appealing owing to its high current intensity and high energy.The medical isotope production based on the proton beam at the CSNS is significant for the development of future radiopharmaceuticals,particularly for theα-emitting radiopharmaceu-ticals.The production yield and activity of typical medical isotopes were estimated using the FLUKA simulation.The results indicate that the 300-MeV proton beam with a power of 100 kW at CSNS-II is highly suitable for proof-of-principle studies of most medical radioisotopes.In particular,this proton beam offers tremendous advantages for the large-scale production of alpha radioisotopes,such as 225Ac,whose theoretical production yield can reach approximately 57 Ci/week.Based on these results,we provide perspectives on the use of CSNS proton beams to produce radioisotopes for medical applications.

Design of 50 MeV proton microbeam based on cyclotron accelerator

High-energy proton microbeam facilities are powerful tools in space science,biology and cancer therapy studies.The primary limitations of the 50 MeV proton microbeam system are the poor beam quality provided by the cyclotron and the problem of intense scattering in the slit position.Here,we present an optical design for a cyclotron-based 50 MeV high-energy proton microbeam system with a micron-sized resolution.The microbeam system,which has an Oxford triplet lens configuration,has relatively small spherical aberrations and is insensitive to changes in the beam divergence angle and momentum spread.In addition,the energy filtration included in the system can reduce the beam momentum spread from 1 to 0.02%.The effects of lens parasitic aberrations and the lens fringe field on the beam spot resolution are also discussed.In addition,owing to the severe scattering of 50 MeV protons in slit materials,a slit system model based on the Geant4 toolkit enables the quantitative analysis of scattered protons and secondary particles.For the slit system settings under a 10-micron final beam spot,very few scattered protons can enter the quadrupole lens system and affect the focusing performance of the microbeam system,but the secondary radiation of neutrons and gamma rays generated at the collimation system should be considered for the 50 MeV proton microbeam.These data demonstrate that a 50 MeV proton microbeam system with a micron-sized beam spot based on a cyclotron is feasible.

Collection efficiency of a monitor parallel plate ionization chamber for pencil beam scanning proton therapy

The collection efficiency of monitor parallel plate ionization chambers is the main uncertainty in the beam control of pencil beam scanning systems.Existing calculation methods for collection efficiency in photon or passive scattering proton systems have not considered the characteristics of non-uniform charge density in pencil beam scanning systems.In this study,Boag’s theory was applied to a proton pencil beam scanning system.The transverse distribution of charge density in the ionization chamber was considered to be a Gaussian function and an analytical solution was derived to calculate collection efficiency in the beam spot area.This calculation method is called the integral method and it was used to investigate the effects of beam parameters on collection efficiency.It was determined that collection efficiency is positively correlated with applied voltage,beam size,and beam energy,but negatively correlated with beam current intensity.Additionally,it was confirmed that collection efficiency is improved when the air filling the monitor parallel plate ionization chamber is replaced with nitrogen.

Continuous operation of 2.45-GHz microwave proton source for 306 hours with more than 50 mA DC beam

This paper describes a long-term operation of the 2.45-GHz microwave proton source at Peking University. The DC proton beam of 50–55 mA with energy of 35 keV has been run for 306 hours continuously. Total beam availability,defined as 35-keV beam-on time divided by elapsed time, is higher than 99%. Water cooling machine failures cause all the downtime, and no plasma generator failure or high voltage breakdown is observed. The longest uninterrupted run time is122 hours.

Reformatted method for two-dimensional detector arrays measurement data in proton pencil beam scanning

The spatial resolution of a commercial two-dimensional(2D)ionization chamber(IC)array is limited by the size of the individual detector and the center-to-center distance between sensors.For dose distributions with areas of steep dose gradients,inter-detector dose values are derived by the interpolation of nearby detector readings in the conventional mathematical interpolation of 2D IC array measurements.This may introduce significant errors,particularly in proton spot scanning radiotherapy.In this study,by combining logfile-based reconstructed dose values and detector measurements with the Laplacian pyramid image blending method,a novel method is proposed to obtain a reformatted dose distribution that provides an improved estimation of the delivered dose distribution with high spatial resolution.Meanwhile,the similarity between the measured original data and the downsampled logfilebased reconstructed dose is regarded as the confidence of the reformatted dose distribution.Furthermore,we quantify the performance benefits of this new approach by directly comparing the reformatted dose distributions with 2D IC array detector mathematically interpolated measurements and original low-resolution measurements.The result shows that this new method is better than the mathematical interpolation and achieves gamma pass rates similar to those of the original low-resolution measurements.The reformatted dose distributions generally yield a confidence exceeding 95%.

Beam charge integration in external beam PIXE–PIGE analysis utilizing proton backscattering with an extraction window

In this study,we present a new method for the indirect integration of beam charges in external beam proton-induced X-ray emission and proton-induced c-ray emission(PIXE–PIGE) analysis.We recorded proton spectra backscattered by a Kapton film extraction window in different sample situations and under different beam currents.We also simulated backscattering spectra using the simulation of backscattering spectra program(SIMNRA).We determined that in a specific geometrical arrangement,different sample situations did not significantly affect factor C_Q(the ratio between integral backscattering proton counts and integral beam charges).We also studied the reproducibility and beam current dependence of factor C_Q.The statistic factor of C_Q was28.95 ± 0.6 kilo counts/l C,with a relative standard deviation of 2.0 %.Significantly,in external beam PIXE–PIGE analysis,we were able to calculate beam charge integration from the integral backscattering proton counts in an energy region.

New progress on beam availability and reliability of PKU high intensity CW proton ECR ion source

The stability and reliability of an ion source and its beam availability are extremely significant for any accelerator,especially for those high current long term CW operation ones like ADS. Although the first high quality 306-hours continuous wave（CW） operating curve at 50 m A@35 ke V has been successfully obtained with a standard compact 2.45 GHz ECR ion source at Peking University（PKU）, but the uncertainties that caused beam trips before are unacceptable during an accelerator real operation and should be eliminated. Meanwhile, no permission will be given when the beam power is upgraded from 50 m A@35 ke V to 50 m A@50 ke V. To improve the PKU CW proton source quality, several upgrades were done recently. After those improvements, a new long term CW proton beam experiment at 50 m A@50 ke V was carried out in June 2016. The total running time is 300.5 hours, including near 6 hours ion source preparation and 294 hours non-disturb continuous operation. Within the continuous 13 days operation, no beam-off happened, no spark was observed,no beam drop appeared, no interrupting action was needed, and only a few beam fluctuations caused by the air conditional failure occurred. Beam availability and reliability within the 294 hours is 100%. The root-mean-square（RMS） emittance of this 50 m A@50 ke V CW proton beam is about 0.186 π.mm.mrad. A careful inspection of the ion source was done after this long term operation and no obvious damage was found. The restart experimental results obtained after the ion source inspection prove the high repeatability of PKU PMECRIS. In addition, a 130-m A H＋beam was obtained at 50 k V with duty factor of 10%（100 Hz/1 ms） with this source. Details will be presented in this paper.

Supercontinuum Generation in Lithium Niobate Ridge Waveguides Fabricated by Proton Exchange and Ion Beam Enhanced Etching

We report on the fabrication of the lO-mm-long lithium niobate ridge waveguide and its supercontinuum gen- eration at near-visible wavelengths （around 800hm）. The waveguides are fabricated by a combination of MeV copper ion implantation followed by wet etching in a proton exchanged lithium niobate planar waveguide. Using a mode-locked Ti：sapphire laser with a central wavelength of 800nm, the generated broadest supereontinuum through the ridge waveguides spans 302 nm （at -30 dB points）, from 693 to 995 nm. Temporal coherence proper- ties of the supercontinuum are experimentally studied by a Michelson interferometer and the coherence length of the broadest supercontinuum is measured to be 5.2 μm. Our results offer potential for a compact and integrated supercontinuum source for applications including bio-imaging, spectroscopy and optical communication.

Generating Proton Beams Exceeding 10 MeV Using High Contrast 60TW Laser

A prototype of a laser driven proton accelerator is built at Peking University. Protons exceeding IOMeV are accelerated from micrometer-thick aluminum targets irradiated by tightly focused laser pulse with 1.8 J energy and 30fs duration. The beam energy spectrum and charge distribution are measured by a Thomson parabola spectrometer and radiochromic fihn stacks. The sensitivity of proton cut-off energy to the focusing of the laser beam, the pulse duration, and the foil thickness are systematically investigated in the experiments. Stable proton beams have been produced with an optimized parameter set, providing a cornerstone for the future applications of laser accelerated protons.

Beam optics study for energy selection system of SC200 superconducting proton cyclotron

To meet the demands on proton therapy in Russia and China, JINR and ASIPP have started to develop a proton therapy facility based on an isochronous superconducting proton accelerator. A 200 Me V/500 n A proton beam will be extracted from the SC200 superconducting proton cyclotron. Due to the energy of the cyclotron being fixed, an energy selection system(ESS) is employed to degrade such energy in order to match the particle energy to a shallower depth. In this article, calculation of beam optics, analysis of beam transmission, and correction of orbit distortion are presented. Studies show that the main factors influencing transmission efficiency of the SC200 ESS beamline are the degrader, collimator, slit, vacuum system, beam diagnostic system, and trajectory correction system. Through the beam optics study, the designed ESS beamline can provide 70–200 Me V proton beam to a treatment room, with a maximum emittance of24 p mm mrad. Also, the controllable momentum spread ranges from 0.1 to 1.0%, which is equivalent to an energy spread from 0.193 to 1.93%. The transmission efficiency about 0.204% can be obtained when the emittance is24 p mm mrad with an energy spread of ± 0.6%.

Numerical Approach of Interactions of Proton Beams and Dense Plasmas with Quantum-Hydrodynamic/Particle-in-Cell Model

A one dimensional quantum-hydrodynamic/particle-in-cell （QHD/PIC） model is used to study the interaction process of an intense proton beam （injection density of 1017 cm-3） with a dense plasma （initial density of -10^21 cm^-3）, with the PIC method for simulating the beam particle dynamics and the QHD model for considering the quantum effects including the quantum statistical and quantum diffraction effects. By means of the QHD theory, the wake electron density and wakefields are calculated, while the proton beam density is calculated by the PIC method and compared to hydrodynamic results to justify that the PIC method is a more suitable way to simulate the beam particle dynamics. The calculation results show that the incident continuous proton beam when propagating in the plasma generates electron perturbations as well as wakefields oscillations with negative valleys and positive peaks where the proton beams are repelled by the positive wakefields and accelerated by the negative wakefields. Moreover, the quantum correction obviously hinders the electron perturbations as well as the wakefields. Therefore, it is necessary to consider the quantum effects in the interaction of a proton beam with cold dense plasmas, such as in the metal films.

Proton beam therapy for locally advanced lung cancer: A review

Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy(PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon(X-ray) radiotherapy(XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk(lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity comparedto XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer.

SAPT:a synchrotron-based proton therapy facility in Shanghai

Because of its excellent dose distribution,proton therapy is becoming increasingly popular in the medical application of cancer treatment.A synchrotron-based proton therapy facility was designed and constructed in Shanghai.The synchrotron,beam delivery system,and other technical systems were commissioned and reached their expected performances.After a clinical trial of 47 patients was finished,the proton therapy facility obtained a registration certificate from the National Medical Products Administration.The characteristics of the accelerator and treatment systems are described in this article.

Proton beam therapy in apneic oxygenation treatment of an unresectable hepatocellular carcinoma: A case report and review of literature

Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tumor had been diagnosed, the patient was immediately treated with proton beam therapy(PBT), at a total dose of 60 Gy(relative biological effectiveness) in 20 fractions administered within 4 wk. To manage the respiratory movements, at the Rinecker Proton Therapy Center, apneic oxygenation was given daily, under general anesthesia. The patient tolerated both the PBT and general anesthesia very well, and did now show any signs of acute or late toxicity. The treatment was followed by constant reductions in the tumor marker alpha-fetoprotein and the cholestatic parameters gamma-glutamyltransferase and alkaline phosphatase. The patient commenced an adjuvant treatment with sorafenib, given at 6-wk intervals, after the PBT. Follow-up with regular magnetic resonance imaging has continued for 40 mo so far, demonstrating remarkable shrinkage of the HCC(maximal diameter dropping from approximately 13 cm to 2 cm). To date, the patient remains free of tumor recurrence. PBT served as a safe and effective treatment method for an unresectable HCC with vascular invasion.

Reirradiation of recurrent breast cancer with proton beam therapy:A case report and literature review

BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities,particularly radiation-induced cardiovascular disease.Reirradiation by proton beam therapy(PBT)enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor.This technology is expected to improve the overall outcome of recurrent breast cancer.CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer.Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy,the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions.Follow-up computed tomography showed a partial remission,without evidence of newly emerging metastasis.At 19 mo after the PBT,the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea,which were successfully treated by drainage and corticosteroid.Cytological analysis of the puncture fluid showed no malignancy,and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions.The patient remains free of progression to date.CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.

Periodic Measurements of Passive Proton Beam Width Using Radiochromic Film in Fixed Gantry System

Background and Aim: Irradiation methods such as double scattering method and spot scanning method have been used in proton beam treatment devices. In the scattering method, a ridge filter or a range modulation wheel is used to create a spread-out Bragg peak, but the distribution at the patient position may change due to positional deviation of the incident beam. Therefore, assessment of the incident position of the beam is very important even in the scattering method. To investigate the width and distribution of the proton beam before entering the RMW, a radiochromic film was installed at the outlet of the transport pipe and the entrance of the profile-monitoring detector. Methods: In this study, the distributions of the beam at the exit of the transport pipe and the entrance of the monitor detector were measured using films. The beam width was measured from the full width at half maximum of the profile obtained from the distribution. Measurements were conducted every month for 10 months. Results: Beams of widths ranging from 1.82 to 2.30 mm in the horizontal direction and 4.25 to 5.33 mm in the vertical direction were outputted from the exit of the transport pipe. Beams of widths ranging from 2.16 to 2.67 mm in the horizontal direction and 4.06 to 5.31 mm in the vertical direction were outputted from the entrance of the monitor detector. The maximum width fluctuation for 10 months was 0.55 mm in the horizontal direction and 1.26 mm in the vertical direction at the entrance of the monitor detector. Conclusions: The distribution was obtained before the proton beam was scattered by the scatterer, and then we propose a method to periodically measure and monitor the changes in the beam distributions every month.

Preliminary Result of Hyperfractionated High-Dose Proton Beam Radiotherapy for Pediatric Skull Base Chordomas

Objective: Proton beam therapy (PBT) may provide good local control for skull base chordoma and reduced toxicities, especially for pediatric patients. Methods: We evaluated the efficacy and safety of hyperfractionated high-dose PBT in6 pediatric patients with newly-diagnosed skull basechordoma who were treated with PBT at our institute from 2011 to 2015. The patients were 5 males and one female, and the median age was 9 years old (range: 5 - 13). All patients received surgery before PBT. The median period between surgery and PBT was 57 days (range: 34 - 129 days). The treatment dose was 78.4 GyE in 56 fractions (twice per day). Results: All patients received PBT without severe acute toxicity. The median follow-up period was 27 months (range: 21 - 71 months). At the last follow-up, all patients were alive and all tumors were well controlled. Acute and late toxicities were generally acceptable, with only grade 1 and 2 events. Late toxicities included growth hormone abnormality and cortical hormone abnormality. One patient needed growth hormone and cortical hormone replacement therapy. Conclusion: Although the number of pediatric patients was small, our overall findings in the 6 cases indicate that hyperfractionated high-dose PBT is safe and effective for pediatric patients with skull base chordoma.

Proton Beam Ocular Treatment in Eyes with Intraocular Silicone Oil: Effects on Physical Beam Parameters and Clinical Relevance of Silicone Oil in EYEPLAN Dose-Volume Histograms

Proton beam therapy (PBRT) is an essential tool in the treatment of certain ocular tumors due to its characteristic fall-off and sharp beam parameters at critical structures. Review of clinical cases in our ocular PBRT program identified patients with silicone oil used as an intraocular tamponade following pars plana vitrectomy for repair of retinal detachment. Patient’s eye may be filled with silicone oil prior to PBRT for an ocular tumor. The objective of this study was to extend our knowledge of the physical characteristics of proton beams in silicone oil by measuring dose within a silicone tank itself, hence better representing the surgical eye, as well as applying the range changes to EYEPLAN software to estimate clinical impact. The relevant proton beam physical parameters in silicone oil were studied using a 67.5 MeV un-modulated proton beam. The beam parameters being defined included: 1) residual range;2) peak/plateau ratio;3) full width at half maximum (FWHM) of the Bragg peak;and 4) distal penumbra. Initially, the dose uniformity of the proton beam was confirmed at 10 mm and 28 mm depth, corresponding to plateau and peak region of the Bragg peak using Gefchromic film. Once the beam was established as expected, three sets of measurements of the beam parameters were taken in: a) water (control);b) silicone-1000 oil and water;and c) silicone-1000 oil only. Central-axis depth-ionization measurements were performed in a tank (“main tank”) with a 0.1cc ionization chamber (Model IC-18, Far west) having walls made of Shonka A150 plastic. The tank was 92 mm (length) × 40 mm (height) × 40 mm (depth). The tank had a 0.13 mm thick kapton entrance window through which the proton beam was incident. The ionization chamber was always positioned in the center of the circular field of diameter 30 mm with the phantom surface at isocenter. The ionization chamber measurements were taken at defined depths in increments of 2 mm, from 0 to 35 mm. To define the effect of silicone oil on the physical characteristics of proton beam, the above-defined three sets of measurements were made. In the first run (a), the Bragg-peak measurements were made in the main tank filled with water. In the second run (b), a second smaller tank filled with 10 mm depth silicone oil was placed in front of the water tank and the measurements were repeated in water. In the third run (c), the water in the main tank was replaced with silicone oil and the measurements were repeated in silicone directly (no second tank in runs “a” and “c”). Finally, the effects of change in range on dose distribution based on the EYEPLAN®treatment planning software of patients with lesions in close proximity to the disc/macula as well as ciliary body tumors were studied. The uniformity of the radiation across the treatment volume shows that the radiation field was uniform within ± 3% at 10 mm depth and within ±4% at 28 mm depth. Parameters evaluated for the three runs (a, b, c) included: 1) residual range;2) peak/plateau ratio;3) FWHM of the Bragg curve;and 4) distal penumbra. The measured data revealed that the un-modulated Bragg peak had a penetration at the isocenter of: a) 30 mm in water;b) 31.5 mm in silicone and water;and c) 32 mm range in silicone oil. The peak/plateau ratio of the depth dose curve is 3.1:1 in all three set-ups. The FWHM is: a) 9 mm in water;b) 10 mm in silicone and water;and c) 11 mm in silicone oil. The distal penumbra (from 90% to 20%) was: a) 1.1 mm;b) 1.4 mm;and c) 2 mm. Clinical relevance of the extended distal range in silicone was studied for impact in EYEPLAN treatment software, including cases in which tumors were in close proximity to the optic disc/nerve and macula as well as cases in which anterior ciliary body tumors were treated. The potential change of range by 2 mm in silicone would impact the dose-volume histograms (DVH) importantly for the posterior structures. In ciliary body/anterior tumors, an increase in distal range in silicone could result in optic disc/macula dose and length of optic nerve treated, compared with original EYEPLAN model DVHs. The use of silicone oil as a surgical tamponade in the treatment of retinal detachments has important implications for PBRT treatment planning. In patients with intraocular silicone oil, the physical parameters of the beam should be closely examined and DVHs for posterior structures should be analyzed for potential increased doses to the macula, disc, and length of optic nerve in the field. The change in beam parameters due to silicone oil is essential to consider in treatment planning and DVH interpretation for ocular patients with posterior as well as anterior ocular tumors.

Robustness Evaluation of a Novel Proton Beam Geometry for Head and Neck Patients Treated with Pencil Beam Scanning Therapy

Background: To evaluate the robustness of head and neck treatment using proton pencil beam scanning (PBS) technique with respect to range uncertainty (RU) and setup errors (SE), and to establish a robust PBS planning strategy for future treatment. Methods and Materials: Ten consecutive patients were planned with a novel proton field geometry (combination of two posterior oblique fields and one anterior field with gradient dose match) using single-field uniform dose (SFUD) planning technique and the proton plans were dosimetrically compared to two coplanar arc VMAT plans. Robustness of the plans, with respect to range uncertainties (RU = ± 3% for proton) and setup errors (SE = 2.25 mm for proton and VMAT), in terms of deviations to target coverage (CTV D98%) and OAR doses (max/mean), were evaluated and compared for each patient under worst case scenarios. Results: Dosimetrically, PBS plans provided better sparing to larynx (p = 0.005), oral cavity (p < 0.001) and contralateral parotid (p = 0.004) when compared to VMAT. CTV D98% variations were higher from SE than from RU for proton plans (-1.1% ± 1.3 % vs -0.4% ± 0.7% for nodal CTV and -1.4% ± 1.2 vs -0.4% ± 0.5% % for boost CTV). Overall, the magnitudes of variation of CTV D98% to combined SE and RU were found to be similar to the impact of the SE on the VMAT plans (-1.6% ± 1.9% vs -1.7% ± 1.4% for nodal CTV and -1.9% ± 1.6% vs -1.3% ± 1.5% for boost CTV). Compared to VMAT, a larger range of relative dose deviations were found for OARs in proton plans, but safe doses were maintained for cord (41.8 ± 3.6 Gy for PBS and 41.7 ± 3.9 Gy for VMAT) and brainstem (35.2 ± 8.4 Gy for PBS and 36.2 ± 5.1 Gy for VMAT) in worst case scenarios. Conclusions: Compared to VMAT, proton plans containing three SFUD fields with superior-inferior gradient dose matching had improved sparing to larynx, contralateral parotid and oral cavity, while providing similar robustness of target coverage. Evaluation of OAR dose robustness showed higher sensitivities to uncertainties for proton plans, but safe dose levels were maintained for cord and brainstem.

Biological Dose Estimation Model for Proton Beam Therapy

Purpose: The recommended value for the relative biological effectiveness (RBE) of proton beams is currently assumed to be 1.1. However, there is increasing evidence that RBE increases towards the end of proton beam range that may increase the biological effect of proton beam in the distal regions of the dose deposition. Methods: A computational approach is presented for estimating the biological effect of the proton beam. It includes a method for calculating the dose averaged linear energy transfer (LET) along the measured Bragg peak and published LET to RBE conversion routine. To validate the proposed method, we have performed Monte Carlo simulations of the pristine Bragg peak at various beam energies and compared the analysis with the simulated results. A good agreement within 5% is observed between the LET analysis of the modeled Bragg peaks and Monte Carlo simulations. Results: Applying the method to the set of Bragg peaks measured at a proton therapy facility we have estimated LET and RBE values along each Bragg peak. Combining the individual RBE-weighted Bragg peaks with known energy modulation weights we have calculated the RBE-weighted dose in the modulated proton beam. The proposed computational method provides a tool for calculating dose averaged LET along the measured Bragg peak. Conclusions: Combined with a model to convert LET into RBE, this method enables calculation of RBE-weighted dose both in pristine Bragg peak and in modulated beam in proton therapy.