Relative Biological Effectiveness Research Articles

Deep learning-based voxel sampling for particle therapy treatment planning

Objective. Scanned particle therapy often requires complex treatment plans, robust optimization, as well as treatment adaptation. Plan optimization is especially complicated for heavy ions due to the variable relative biological effectiveness. We present a novel deep-learning model to select a subset of voxels in the planning process thus reducing the planning problem size for improved computational efficiency. Approach. Using only a subset of the voxels in target and organs at risk (OARs) we produced high-quality treatment plans, but heuristic selection strategies require manual input. We designed a deep-learning model based on P-Net to obtain an optimal voxel sampling without relying on patient-specific user input. A cohort of 70 head and neck patients that received carbon ion therapy was used for model training (50), validation (10) and testing (10). For training, a total of 12 500 carbon ion plans were optimized, using a highly efficient artificial intelligence (AI) infrastructure implemented into a research treatment planning platform. A custom loss function increased sampling density in underdosed regions, while aiming to reduce the total number of voxels. Main results. On the test dataset, the number of voxels in the optimization could be reduced by 84.8% (median) at <1% median loss in plan quality. When the model was trained to reduce sampling in the target only while keeping all voxels in OARs, a median reduction up to 71.6% was achieved, with 0.5% loss in the plan quality. The optimization time was reduced by a factor of 7.5 for the total AI selection model and a factor of 3.7 for the model with only target selection. Significance. The novel deep-learning voxel sampling technique achieves a significant reduction in computational time with a negligible loss in the plan quality. The reduction in optimization time can be especially useful for future real-time adaptation strategies.

A deep-learning-based surrogate model for Monte-Carlo simulations of the linear energy transfer in primary brain tumor patients treated with proton-beam radiotherapy.

This study explores the use of neural networks (NNs) as surrogate models for Monte-Carlo (MC) simulations in predicting the dose-averaged linear energy transfer (LETd) of protons in proton-beam therapy based on the planned dose distribution and patient anatomy in the form of computed tomography (CT) images. As LETdis associated with variability in the relative biological effectiveness (RBE) of protons, we also evaluate the implications of using NN predictions for normal tissue complication probability (NTCP) models within a variable-RBE context.&#xD;&#xD;Approach: The predictive performance of three-dimensional NN architectures was evaluated using five-fold cross-validation on a cohort of brain tumor patients (n=151). The best-performing model was identified and externally validated on patients from a different center (n=107). LETdpredictions were compared to MC-simulated results in clinically relevant regions of interest. We assessed the impact on NTCP models by leveraging LETdpredictions to derive RBE-weighted doses, using the Wedenberg RBE model.&#xD;&#xD;Main results: We found NNs based solely on the planned dose profile, i.e. without additional usage of CT images, can approximate MC-based LETddistributions. Root mean squared errors (RMSE) for the median LETdwithin the brain, brainstem, CTV, chiasm, lacrimal glands (ipsilateral/contralateral) and optic nerves (ipsilateral/contralateral) were 0.36, 0.87, 0.31, 0.73, 0.68, 1.04, 0.69 and 1.24~keV/μm, respectively. Although model predictions showed statistically significant differences from MC outputs, these did not result in substantial changes in NTCP predictions, with RMSEs of at most 3.2 percentage points.&#xD;&#xD;Significance: The ability of NNs to predict LETdbased solely on planned dose profiles suggests a viable alternative to the compute-intensive MC simulations in a variable-RBE setting. This is particularly useful in scenarios where MC simulation data are unavailable, facilitating resource-constrained proton therapy treatment planning, retrospective patient data analysis and further investigations on the variability of proton RBE.

Incorporating boron distribution variations in microdosimetric kinetic model-based relative biological effectiveness calculations for boron neutron capture therapy.

This study introduces the MKM_B model, an approach derived from the MKM model, designed to evaluate the biological effectiveness of Boron Neutron Capture Therapy (BNCT) in the face of challenges from varying microscopic boron distributions. The model introduces a boron compensation factor, allowing for the assessment of compound Biological Effectiveness (CBE) values for different boron distributions. Utilizing the TOPAS simulation platform, the lineal energy spectrum of particles in BNCT was simulated, and the sensitivity of the MKM_B model to parameter variations and the influence of cell size on the model were thoroughly investigated. The CBE values for 10B-boronphenylalanine (BPA) and 10B-sodium (BSH) were determined to be 3.70 and 1.75, respectively. These calculations were based on using the nucleus radius of 2.5 μm and the cell radius of 5 μm while considering a 50% surviving fraction. It was observed that as cell size decreased, the CBE values for both BPA and BSH increased. Additionally, the model parameter rd was identified as having the most significant impact on CBE, with other parameters showing moderate effects. The development of the MKM_B model enables the accurate prediction of CBE under different boron distributions in BNCT. This model offers a promising approach to optimize treatment planning by providing increased accuracy in biological effectiveness.

Comparative Evaluation of Two Analytical Functions for the Microdosimetry of Ions from 1H to 238U

The analytical microdosimetric function (AMF) implemented in the Monte Carlo code PHITS is a unique tool that bridges the gap between macro- and microscopic scales of radiation interactions, enabling accurate microdosimetric calculations over macroscopic bodies. The original AMF was published in 2006, based on the results of track structure calculations. Recently, a newer version of the AMF was proposed, incorporating an improved description of the energy loss at the microscopic scale. This study compares the older and the newer AMFs in computing microdosimetric probability distributions, mean values, and the relative biological effectiveness (RBE). To this end, 16,000 microdosimetric lineal energy probability density distributions were simulated with PHITS for ions from 1H to 238U over a broad energy range (1–1000 MeV/n). The newer AMF was found to offer superior performance, particularly for very heavy ions, producing results that align more closely with published in vitro clonogenic survival experiments. These findings suggest that the updated AMF provides a more reliable tool for microdosimetric calculations and RBE modeling, essential for ion radiation therapy and space radiation protection.

Quantifying the Dosimetric Impact of Proton Range Uncertainties on RBE-Weighted Dose Distributions in Intensity-Modulated Proton Therapy for Bilateral Head and Neck Cancer

Background: In current clinical practice, intensity-modulated proton therapy (IMPT) head and neck cancer (HNC) plans are generated using a constant relative biological effectiveness (cRBE) of 1.1. The primary goal of this study was to explore the dosimetric impact of proton range uncertainties on RBE-weighted dose (RWD) distributions using a variable RBE (vRBE) model in the context of bilateral HNC IMPT plans. Methods: The current study included the computed tomography (CT) datasets of ten bilateral HNC patients who had undergone photon therapy. Each patient’s plan was generated using three IMPT beams to deliver doses to the CTV_High and CTV_Low for doses of 70 Gy(RBE) and 54 Gy(RBE), respectively, in 35 fractions through a simultaneous integrated boost (SIB) technique. Each nominal plan calculated with a cRBE of 1.1 was subjected to the range uncertainties of ±3%. The McNamara vRBE model was used for RWD calculations. For each patient, the differences in dosimetric metrices between the RWD and nominal dose distributions were compared. Results: The constrictor muscles, oral cavity, parotids, larynx, thyroid, and esophagus showed average differences in mean dose (Dmean) values up to 6.91 Gy(RBE), indicating the impact of proton range uncertainties on RWD distributions. Similarly, the brachial plexus, brain, brainstem, spinal cord, and mandible showed varying degrees of the average differences in maximum dose (Dmax) values (2.78–10.75 Gy(RBE)). The Dmean and Dmax to the CTV from RWD distributions were within ±2% of the dosimetric results in nominal plans. Conclusion: The consistent trend of higher mean and maximum doses to the OARs with the McNamara vRBE model compared to cRBE model highlighted the need for consideration of proton range uncertainties while evaluating OAR doses in bilateral HNC IMPT plans.

Research Trends in the Study of the Relative Biological Effectiveness: A Bibliometric Study.

The relative biological effectiveness is a mathematical quantity first defined in the 1950s. This has resulted in more than 4,000 scientific papers published to date. Yet defining the correct value of the RBE to use in clinical practice remains a challenge. A scientific analysis in the radiation research literature can provide an understanding of how this mathematical quantity has evolved. The purpose of this study is to investigate documents published since 1950 using bibliometric indicators and network visualization. This analysis seeks to provide an assessment of global research activities, key themes, and RBE research within the radiation-related field. It strives to highlight top-performing authors, organizations, and nations that have made major contributions to this research domain, as well as their interactions. The Scopus Collection was searched for articles and reviews pertaining to RBE in radiation research from 1950 through 2023. Scopus and Bibiometrix analytic tools were used to investigate the most productive countries, researchers, collaboration networks, journals, along with the citation analysis of references and keywords. A total of 4,632 documents were retrieved produced by authors originating from 71 countries. Publication trends could be separated in 20-year groupings beginning with slow accrual from 1950 to 1970, an early rise from 1970-1990, followed by a sharp increase in the years 1990s-2010s that matches the development of charged particle therapy in clinics worldwide and opened discussion on the true value of the RBE in proton beam therapy. Since the 2010s, a steady 200 papers, on average, have been published per year. The United States produced the most publications overall (N = 1,378) and Radiation Research was the most likely journal to have published articles related to the RBE (606 publications during this period). J. Debus was the most prolific author (112 contributions, with 2,900 citations). The RBE has captured the research interest of over 7,000 authors in the past decade alone. This study supports that notion that the growth of the body of evidence surrounding the RBE, which started 75 years ago, is far from reaching its end. Applications to medicine have continuously dominated the field, with physics competing with Biochemistry, Genetics and Molecular Biology for second place over the decades. Future research can be predicted to continue.

Proton therapy for intracranial meningioma: a single-institution retrospective analysis of efficacy, survival and toxicity outcomes.

To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.

An updated variable RBE model for proton therapy

Objective. While a constant relative biological effectiveness (RBE) of 1.1 forms the basis for clinical proton therapy, variable RBE models are increasingly being used in plan evaluation. However, there is substantial variation across RBE models, and several new in vitro datasets have not yet been included in the existing models. In this study, an updated in vitro proton RBE database was collected and used to examine current RBE model assumptions, and to propose an up-to-date RBE model as a tool for evaluating RBE effects in clinical settings. Approach. A proton database (471 data points) was collected from the literature, almost twice the size of the previously largest model database. Each data point included linear-quadratic model parameters and linear energy transfer (LET). Statistical analyses were performed to test the validity of commonly applied assumptions of phenomenological RBE models, and new model functions were proposed for RBEmax and RBEmin (RBE at the lower and upper dose limits). Previously published models were refitted to the database and compared to the new model in terms of model performance and RBE estimates. Main results. The statistical analysis indicated that the intercept of the RBEmax function should be a free fitting parameter and RBE estimates were clearly higher for models with free intercept. RBEmin increased with increasing LET, while a dependency of RBEmin on the reference radiation fractionation sensitivity ( α/βx ) did not significantly improve model performance. Evaluating the models, the new model gave overall lowest RMSE and highest R2 score. RBE estimates in the distal part of a spread-out-Bragg-peak in water ( α/βx = 2.1 Gy) were 1.24–1.51 for original models, 1.25–1.49 for refits and 1.42 for the new model. Significance. An updated RBE model based on the currently largest database among published phenomenological models was proposed. Overall, the new model showed better performance compared to refitted published RBE models.

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams

Objective. This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer ( LET― ) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations. Approach. Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities. For each irradiation, the fluence- ( LET―f ) and dose-averaged LET ( LET―d ) were determined. For both quantities, two sub-types of averages were calculated, either considering the contributions from primary and secondary protons or from all protons and heavier, charged particles. Both simulated and experimental data were used in combination with a phenomenological model to estimate the relative biological effectiveness (RBE). Main results. All types of LET― could be assessed with the luminescence detectors. The experimental determination of LET―f is in agreement with reference data obtained from simulations across all measurement techniques and types of averaging. On the other hand, LET―d can present challenges as a radiation quality metric to describe the detector response in mixed particle fields. However, excluding secondaries heavier than protons from the LET―d calculation, as their contribution to the luminescence is suppressed by ionization quenching, leads to equal accuracy between LET―f and LET―d . Assessment of RBE through the experimentally determined LET―d values agrees with independently acquired reference values, indicating that the investigated detectors can determine LET― with sufficient accuracy for proton therapy. Significance. OSLDs, TLDs, and FNTDs can be used to determine LET― and RBE in proton therapy. With the capability to determine dose through ionization quenching corrections derived from LET― , OSLDs and TLDs can simultaneously ascertain dose, LET― , and RBE. This makes passive detectors appealing for measurements in phantoms to facilitate validation of clinical treatment plans or experiments related to proton therapy.

Preliminary result of combined treatment with scanning carbon-ion radiotherapy and image-guided brachytherapy for locally advanced cervical adenocarcinoma.

Although there is growing evidence of the efficacy of carbon-ion radiotherapy (CIRT) for locally advanced cervical adenocarcinoma, reports on combined treatment with CIRT and image-guided brachytherapy (IGBT) are scarce. We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (2008) stage II-IVA locally advanced cervical adenocarcinoma who received combined scanning CIRT (sCIRT) and IGBT between April 2019 and March 2022. sCIRT consisted of whole-pelvic irradiation with 36Gy (relative biological effectiveness [RBE]) in 12 fractions and subsequent local boost irradiation with 19.2Gy (RBE) in 4 fractions. Three sessions of IGBT were administered after completion of sCIRT. Concurrent chemotherapy using weekly cisplatin (40mg/m2/week) was also administered. Efficacy, toxicity and dose-volume parameters were analyzed. Fifteen patients were included in the analysis. The median follow-up period was 25months. The 2-year overall survival, progression-free survival and local control rates were 92.3% (95% confidence interval [CI] = 77.8-100%), 52.5% (95% CI = 26.9-78.1%) and 84.8% (95% CI = 65.2-100%), respectively. Neither severe acute toxicity necessitating treatment cessation nor grade 3 or higher late toxicity were observed. The sigmoid D2cm3 of the patient who developed grade 2 late sigmoid hemorrhage was 65.6Gy, which exceeded the standard deviation and target dose. The combination of sCIRT and IGBT for locally advanced cervical adenocarcinoma showed acceptable efficacy and safety. Further large-scale and long-term studies are warranted to confirm the efficacy and safety of this treatment.

Deep learning based linear energy transfer calculation for proton therapy

Objective. This study aims to address the limitations of traditional methods for calculating linear energy transfer (LET), a critical component in assessing relative biological effectiveness (RBE). Currently, Monte Carlo (MC) simulation, the gold-standard for accuracy, is resource-intensive and slow for dose optimization, while the speedier analytical approximation has compromised accuracy. Our objective was to prototype a deep-learning-based model for calculating dose-averaged LET (LETd) using patient anatomy and dose-to-water (DW) data, facilitating real-time biological dose evaluation and LET optimization within proton treatment planning systems. Approach. 275 4-field prostate proton Stereotactic Body Radiotherapy plans were analyzed, rendering a total of 1100 fields. Those were randomly split into 880, 110, and 110 fields for training, validation, and testing. A 3D Cascaded UNet model, along with data processing and inference pipelines, was developed to generate patient-specific LETd distributions from CT images and DW. The accuracy of the LETd of the test dataset was evaluated against MC-generated ground truth through voxel-based mean absolute error (MAE) and gamma analysis. Main results. The proposed model accurately inferred LETd distributions for each proton field in the test dataset. A single-field LETd calculation took around 100 ms with trained models running on a NVidia A100 GPU. The selected model yielded an average MAE of 0.94 ± 0.14 MeV cm−1 and a gamma passing rate of 97.4% ± 1.3% when applied to the test dataset, with the largest discrepancy at the edge of fields where the dose gradient was the largest and counting statistics was the lowest. Significance. This study demonstrates that deep-learning-based models can efficiently calculate LETd with high accuracy as a fast-forward approach. The model shows great potential to be utilized for optimizing the RBE of proton treatment plans. Future efforts will focus on enhancing the model’s performance and evaluating its adaptability to different clinical scenarios.

Outcomes of definitive carbon-ion radiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

A recent phase I/II study determined the optimal dose of definitive carbon-ion radiotherapy (CIRT) for cT1bN0M0 esophageal cancer. This study aimed to further confirm the efficacy and feasibility of the recommended dose fractionation of CIRT with long-term follow-up results in a larger sample size. This single center retrospective study evaluated patients with cT1bN0M0 esophageal squamous cell carcinoma treated with the recommended dose fractionation of 50.4Gy relative biological effectiveness in 12 fractions, between 2012 and 2022. Thirty-eight patients underwent CIRT at our hospital. Although eight (21.1%) patients were older than 80years, 15 (39.5%) had high surgical risk, and seven (18.4%) were at high risk for chemotherapy, all patients underwent CIRT as scheduled. Grade 3 esophagitis occurred in eight (21.1%) patients and grade 3 pneumonia in one (2.6%) patient in this study, but no grade 4 adverse events occurred. The only grade 3 late adverse event was pneumonia in one patient (2.6%). The 5-year overall survival rate, local control rate, and disease-free survival rates were 76.6% (95% CI, 90.9-62.4), 74.9% (95% CI, 90.7-59.0), and 66.4% (95% CI, 83.3-49.5), respectively. Additionally, post CIRT recurrence was as follows: seven (18.4%) patients had recurrence in another part of the esophagus, three (7.9%) in the primary site, three (7.9%) in lymph nodes outside the irradiated area, and one (2.6%) patient had liver metastasis. Our study demonstrates that CIRT using the recommended dose fractionation is feasible and effective for cT1bN0M0 esophageal squamous cell carcinoma.

Helium Ion Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma.

Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications.

Biological dose optimization incorporating intra-tumoural cellular radiosensitivity heterogeneity in ion-beam therapy treatment planning

Objective. Treatment plans of ion-beam therapy have been made under an assumption that all cancer cells within a tumour equally respond to a given radiation dose. However, an intra-tumoural cellular radiosensitivity heterogeneity clearly exists, and it may lead to an overestimation of therapeutic effects of the radiation. The purpose of this study is to develop a biological model that can incorporate the radiosensitivity heterogeneity into biological optimization for ion-beam therapy treatment planning. Approach. The radiosensitivity heterogeneity was modeled as the variability of a cell-line specific parameter in the microdosimetric kinetic model following the gamma distribution. To validate the developed intra-tumoural-radiosensitivity-heterogeneity-incorporated microdosimetric kinetic (HMK) model, a treatment plan with H-ion beams was made for a chordoma case, assuming a radiosensitivity heterogeneous region within the tumour. To investigate the effects of the radiosensitivity heterogeneity on the biological effectiveness of H-, He-, C-, O-, and Ne-ion beams, the relative biological effectiveness (RBE)-weighted dose distributions were planned for a cuboid target with the stated ion beams without considering the heterogeneity. The planned dose distributions were then recalculated by taking the heterogeneity into account. Main results. The cell survival fraction and corresponding RBE-weighted dose were formulated based on the HMK model. The first derivative of the RBE-weighted dose distribution was also derived, which is needed for fast biological optimization. For the patient plan, the biological optimization increased the dose to the radiosensitivity heterogeneous region to compensate for the heterogeneity-induced reduction in biological effectiveness of the H-ion beams. The reduction in biological effectiveness due to the heterogeneity was pronounced for low linear energy transfer (LET) beams but moderate for high-LET beams. The RBE-weighted dose in the cuboid target decreased by 7.6% for the H-ion beam, while it decreased by just 1.4% for the Ne-ion beam. Significance. Optimal treatment plans that consider intra-tumoural cellular radiosensitivity heterogeneity can be devised using the HMK model.

DNA-damage RBE assessment for combined boron and gadolinium neutron capture therapy.

Neutron capture therapy (NCT) by 10B and 157Gd agents is a unique irradiation-based method which can be used to treat brain tumors. Current study aims to quantitatively evaluate the relative biological effectiveness (RBE) and dose distributions during the combined BNCT and GdNCT modalities through a hybrid Monte Carlo (MC) simulation approach. Snyder head phantom as well as a cubic hypothetical tumor was at first modeled by Geant4 MC Code. Then, the energy spectra and dose distribution relevant to the released secondary particles during the combined Gd/BNCT were scored for different concentrations of 157Gd and 10B inside tumor volume. Finally, the scored energy spectra were imported to the MCDS code to estimate both RBESSB and RBEDSB values for different 157Gd concentrations. The results showed that combined Gd/BNCT increases the fluence-averaged RBESSB values by about 1.7 times when 157Gd concentration increments from 0 to 2000µg/g for both considered cell oxygen levels (pO2=10% and 100%). Besides, a reduction of about 26% was found for fluence-averaged RBEDSB values with an increment of 157Gd concentration in tumor volume. From the results, it can be concluded that combined Gd/BNCT technique can improve tumor coverage with higher dose levels but in the expense of RBEDSB reduction which can affect the clinical efficacy of the NCT technique.

First in vitro measurement of VHEE relative biological effectiveness (RBE) in lung and prostate cancer cells using the ARES linac at DESY

Very high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE to inhomogeneities. This study explores how electrons in the VHEE range can be used to perform successful in vitro radiobiological studies. The ARES (accelerator research experiment at SINBAD) facility at DESY, Hamburg, Germany was used to deliver 154 MeV electrons to both prostate (PC3) and lung (A549) cancer cells in suspension. Dose was delivered to samples with repeatability and uniformity, quantified with Gafchromic film. Cell survival in response to VHEE was measured using the clonogenic assay to determine the biological effectiveness of VHEE in cancer cells for the first time using this method. Equivalent experiments were performed using 300 kVp X-rays, to enable VHEE irradiated cells to be compared with conventional photons. VHEE irradiated cancer cell survival was fitted to the linear quadratic (LQ) model (R2 = 0.96–0.97). The damage from VHEE and X-ray irradiated cells at doses between 1.41 and 6.33 Gy are comparable, suggesting similar relative biological effectiveness (RBE) between the two modalities. This suggests VHEE is as damaging as photon radiotherapy and therefore could be used to successfully damage cancer cells during radiotherapy. The RBE of VHEE was quantified as the relative doses required for 50% (D0.5) and 10% (D0.1) cell survival. Using these values, VHEE RBE was measured as 0.93 (D0.5) and 0.99 (D0.1) for A549 and 0.74 (D0.5) and 0.93 (D0.1) for PC3 cell lines respectively. For the first time, this study has shown that 154 MeV electrons can be used to effectively kill lung and prostate cancer cells, suggesting that VHEE would be a viable radiotherapy modality. Several studies have shown that VHEE has characteristics that would offer significant improvements over conventional photon radiotherapy for example, electrons are relatively easy to steer and can be used to deliver dose rapidly and with high efficiency. Studies have shown improved dose distribution with VHEE in treatment plans, in comparison to VMAT, indicating that VHEE can offer improved and safer treatment plans with reduced side effects. The biological response of cancer cells to VHEE has not been sufficiently studied as of yet, however this initial study provides some initial insights into cell damage. VHEE offers significant benefits over photon radiotherapy and therefore more studies are required to fully understand the biological effectiveness of VHEE.

Moderately hypofractionated proton beam therapy for localized prostate cancer: 5-year outcomes of a phase II trial.

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96months (range: 60-119months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1-6.9) and 4% (95% CI: 1.5-10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70Gy (RBE) in 28 fractions, indicating the safety of this schedule.

A review and bibliometric analysis of global research on proton radiotherapy.

Proton beam therapy (PBT) has great advantages as tumor radiotherapy and is progressively becoming a more prevalent choice for individuals undergoing radiation therapy. The objective of this review is to pinpoint collaborative efforts among countries and institutions, while also exploring the hot topics and future outlook in the field of PBT. Data from publications were downloaded from the Web of Science Core Collection. CiteSpace and Excel 2016 were used to conduct the bibliometric and knowledge map analysis. A total of 6516 publications were identified, with the total number of articles steadily increasing and the United States being the most productive country. Harvard University took the lead in contributing the highest number of publications. Paganetti Harald published the most articles and had the most cocitations. PHYS MED BIOL published the greatest number of PBT-related articles, while INT J RADIAT ONCOL received the most citations. Paganetti Harald, 2012, PHYS MED BIOL can be classified as classic literature due to its high citation rate. We believe that research on technology development, dose calculation and relative biological effectiveness were the knowledge bases in this field. Future research hotspots may include clinical trials, flash radiotherapy, and immunotherapy.

Carbon ion radiotherapy for mesonephric adenocarcinoma of the uterine cervix: a case report

BackgroundMesonephric adenocarcinoma is an extremely rare subtype of uterine cervical cancer that is associated with a poor prognosis and for which a standardized treatment protocol has not been established. Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality that has been shown to have a favorable anti-tumor effect, even for tumors resistant to conventional photon radiotherapy or chemotherapy. However, there is no report on CIRT outcomes for mesonephric adenocarcinoma of the uterine cervix.Case presentationWe treated a 47-year-old Japanese woman with mesonephric adenocarcinoma of the uterine cervix (T2bN0M0 and stage IIB according to the 7th edition of the Union for International Cancer Control and International Federation of Gynecology and Obstetrics, respectively) with CIRT combined with brachytherapy and concurrent chemotherapy. CIRT consisted of whole pelvic irradiation and boost irradiation to the gross tumor; 36.0 Gy (relative biological effectiveness [RBE]) in 12 fractions and 19.2 Gy (RBE) in 4 fractions, respectively, performed once a day, four times per week. Computed tomography-based image-guided adaptive brachytherapy was performed after completion of CIRT, for which the D90 (i.e., the dose prescribed to 90% of the target volume) for the high-risk clinical target volume was 20.4 Gy in a total of 3 sessions in 2 weeks. A weekly cisplatin (40 mg/m2) dose was administered concomitantly with the radiotherapy for a total of five courses. From 4 months post-CIRT, the patient developed metastasis of the lung, with a total of 10 lung metastases over 70 months; these lesions were treated on each occasion by photon stereotactic body radiotherapy and/or systemic therapy. At 8 years from initial treatment (i.e., 2 years after the last treatment), the patient is alive without any evidence of recurrence and maintains a high quality of life.ConclusionsThis is the first report of CIRT for treatment of mesonephric adenocarcinoma of the uterine cervix. The present case indicates the potential efficacy of CIRT in combination with brachytherapy for treatment of this disease.

Alanine dosimeters for LET measurement in proton radiotherapy

Proton radiotherapy enables highly conformal dose delivery to the tumor while minimizing exposure to healthy tissues surrounding the target. However, to achieve the most optimal treatment plan, it is necessary to consider various parameters, including variable relative biological effectiveness (RBE) and linear energy transfer (LET) within the target and in the normal tissues. The proton treatment planning systems (TPS) currently under development incorporate both of these parameters. However, before introducing biologically guided treatment planning into the clinic, commissioning and end-to-end tests must be conducted. These procedures require specific tools to verify the planned LET distribution. The same tools will also be necessary for subsequent patient-specific quality assurance (QA).The objective of this work was to evaluate the alanine/EPR dosimetry system developed at the Cyclotron Center Bronowice at the Institute of Nuclear Physics (CCB IFJ PAN) for verifying LET values in therapeutic proton fields. The change in the shape of the EPR spectra of alanine irradiated in proton fields of different LETs, described by the ratio of the intensities of the satellite and central lines (x/y ratio), was used to discriminate LET values. The method does not provide absolute LET values. However, as demonstrated, it can verify the LET values calculated in the TPS after calibration using Monte Carlo (MC) simulation.