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This work aims at reviewing challenges and pitfalls in proton facility design related to equipment upgrade or replacement. Proton therapy was initially developed at research institutions in the 1950s which ushered in the use of hospital-based machines in 1990s. We are approaching an era where older commercial machines are reaching the end of their life and require replacement. The future widespread application of proton therapy depends on cost reduction; customized building design and installation are significant expenses. We take this opportunity to discuss how commercial proton machines have been installed and how buildings housing the equipment have been designed. Data on dimensions and weights of the larger components of proton systems (cyclotron main magnet and gantries) are presented and innovative, non-gantry-based, patient positioning systems are discussed. We argue that careful consideration of the building design to include larger elevators, hoistways from above, wide corridors and access slopes to below grade installations, generic vault and treatment room layouts to accommodate multiple vendor's equipment, and modular system design can provide specific benefits during planning, installation, maintenance, and replacement phases of the project. Room temperature magnet coils can be constructed in a more modular manner: a potential configuration is presented. There is scope for constructing gantries and magnet yokes from smaller modular sub-units. These considerations would allow a hospital to replace a commercial machine at its end of life in a manner similar to a linac. [ABSTRACT FROM AUTHOR]

• Examines effect of voxel intensity binning range on radiomic feature stability. • First multi-energy systematic study of its kind, describing detailed methodology. • Uses radiomic features benchmarked by Image Biomarker Standardization Initiative. • Presents empirical method for determining optimal re-segmentation range for a dataset. • Methodology can be adopted by other researchers to improve replicability. Radiomic texture calculation requires discretizing image intensities within the region-of-interest. FBN (fixed-bin-number), FBS (fixed-bin-size) and FBN and FBS with intensity equalization (FBNequal, FBSequal) are four discretization approaches. A crucial choice is the voxel intensity (Hounsfield units, or HU) binning range. We assessed the effect of this choice on radiomic features. The dataset comprised 95 patients with head-and-neck squamous-cell-carcinoma. Dual energy CT data was reconstructed at 21 electron energies (40, 45,... 140 keV). Each of 94 texture features were calculated with 64 extraction parameters. All features were calculated five times: original choice, left shift (-10/-20 HU), right shift (+10/+20 HU). For each feature, Spearman correlation between nominal and four variants were calculated to determine feature stability. This was done for six texture feature types (GLCM, GLRLM, GLSZM, GLDZM, NGTDM, and NGLDM) separately. This analysis was repeated for the four binning algorithms. Effect of feature instability on predictive ability was studied for lymphadenopathy as endpoint. FBN and FBNequal algorithms showed good stability (correlation values consistently > 0.9). For FBS and FBSequal algorithms, while median values exceeded 0.9, the 95% lower bound decreased as a function of energy, with poor performance over the entire spectrum. FBNequal was the most stable algorithm, and FBS the least. We believe this is the first multi-energy systematic study of the impact of CT HU range used during intensity discretization for radiomic feature extraction. Future analyses should account for this source of uncertainty when evaluating the robustness of their radiomic signature. [ABSTRACT FROM AUTHOR]

• The egs_chamber determined the field output correction factors of RPLGD and CC01. • The field output correction factors were validated against IAEA-AAPM TRS-483. • The parallel orientation improved the small field output factors of RPLGD. • The volume averaging effect was small for RPLGD in parallel orientation. • RPLGD in parallel orientation is practical for field sizes down to 0.6 × 0.6 cm2. To determine the field output correction factors of the radiophotoluminescence glass dosimeter (RPLGD) in parallel and perpendicular orientations with reference to CC01, the ionization chamber. The dose to a small water volume and the sensitive volume of the RPLGD and the IBA-CC01 were determined for 6-MV, 100-cm SAD, 10-cm depth using egs_chamber user-code. The RPLGD in perpendicular and parallel orientations to the beam axis were studied. The field output correction factors of each detector for 0.5 × 0.5 to 10 × 10 cm2 field sizes were determined. These field output correction factors were validated by comparing field output factors against data determined from IAEA-AAPM TRS-483 code of practice. The field output correction factors of all detectors were within 5% for field sizes down to 0.8 × 0.8 cm2. For 0.5 × 0.5 cm2, the field output correction factors of CC01, RPLGD in perpendicular and parallel orientations differed from unity by 14%, 19%, and 5%, respectively. The percentage difference between field output factors determined using RPLGD and CC01 data, corrected using the field output correction factors determined in this work and measurements with CC01 data corrected using TRS-483, was less than 3% for all field sizes, except for the smallest field size of RPLGD in perpendicular orientation and the CC01. The field output correction factors of RPLGD and CC01 are reported. The validation proves that RPLGD in parallel orientation combined with the field output correction factors is the most suitable for determining the field output factors for the smallest field used in this study. [ABSTRACT FROM AUTHOR]

Intraoperative radiation therapy (IORT) using the INTRABEAM, a miniature x-ray source, has shown to be effective in treating breast cancer. However, recent investigations have suggested a significant deviation between the reported and delivered doses. In this work, the dose delivered by INTRABEAM in the TARGIT breast protocol was investigated, along with the dose from the Xoft Axxent, another source used in breast IORT. The absorbed dose from the INTRABEAM was determined from ionization chamber measurements using: (a) the manufacturer-recommended formula (Zeiss V4.0 method), (b) a Monte Carlo calculated chamber conversion factor (C Q method), and (c) the formula consistent with the TARGIT breast protocol (TARGIT method). The dose from the Xoft Axxent was determined from ionization chamber measurements using the Zeiss V4.0 method and calculated using the American Association of Physicists in Medicine TG-43 formalism. For a nominal TARGIT prescription of 20 Gy, the dose at the INTRABEAM applicator surface ranged from 25.2 to 31.7 Gy according to the C Q method for the largest (5 cm) and smallest (1.5 cm) diameter applicator, respectively. The Zeiss V4.0 method results were 7% to 10% lower (23.2 to 28.6 Gy). At 1 cm depth, the C Q and Zeiss V4.0 absorbed doses were also larger than those predicted by the TARGIT method. The dose at 1 cm depth from the Xoft Axxent for a surface dose of 20 Gy was slightly less than INTRABEAM (3%-7% compared with C Q method). An exception was for the 3 cm applicator, where the Xoft dose was appreciably lower (31%). The doses delivered in the TARGIT breast protocol with INTRABEAM were significantly greater than the prescribed 20 Gy and depended on the size of spherical applicator used. Breast IORT treatments with the Xoft Axxent received less dose compared with TARGIT INTRABEAM, which could have implications for studies comparing clinical outcomes between the 2 devices. [ABSTRACT FROM AUTHOR]

• Step-size correction is implemented in EGSnrc-based Cherenkov Monte Carlo. • A simplified method yields up to 3% step-size effect with photons and electrons. • A new method yields negligible (0.1%) step-size effect on Cherenkov Monte Carlo. Purpose: Previous work presented and validated in-water Cherenkov emission (CE)-based radiotherapy dosimetry. Condensed history Monte Carlo (MC)-calculated electron beam CE-to-dose conversion with < 4 π CE detection, however, could exhibit step-size dependence. This work presents a physics update and numerical study of this step-size dependence in photon and electron beams, elucidates the CE generation physics, and guides further research. Methods: The CE-to-dose conversion, k C θ ± δ θ , is calculated for photons (6X, 15X) and electrons (6E, 20E) on-axis in-water with: θ ± δ θ ∈ { 90 ° ± 90 ° (4 π) , 90 ° ± 5 ° , 45 ° ± 45 ° , 90 ° ± 45 ° } , 10 cm equivalent square, 100 cm SSD, 1cm voxel radius and beam-dependent length. Relative deviation from single-scattering (SS) simulation is evaluated on maximum fractional electron step energy loss ESTEPE ∈ 0.01 - 0.25 . Standard uncertainties (k = 1 , 10 8 histories) are reported. A simplified method considering only the straight step direction is also implemented. Results: No significant step-size effect (> 0.1 %) was observed for dose and all k C θ ± δ θ , except for surface dosimetry at 90 ° ± 5 ° (- 1.6 % ± 0.5 % , 20E), which is not recommended. Electron SS deviation uncertainties (k = 1), otherwise, varied from < 0.2 % overall to < 0.1 % with large apertures. Photon uncertainties varied from < 1.1 % overall to < 0.2 % non-superficially with large apertures. The simplified straight-step method exhibited overall greater deviation from SS, most notably - 2.8 % ± 0.1 % (6E) and - 2.5 % ± 0.4 % (20E) superficially with 90 ° ± 45 ° , and - 1.4 % ± 0.3 % (6X) and - 0.6 % ± 0.2 % (15X) non-superficially with 90 ° ± 5 ° for ESTEPE ∈ 0.10 , 0.25 . Conclusions: We demonstrate step-size independence of newly-implemented correction in EGSnrc directional Cherenkov calculations. This advances clinical CE-based dosimetry and is useful for the general Monte Carlo community. [ABSTRACT FROM AUTHOR]

• Monte Carlo recalculation of 219 CyberKnife lung SBRT plans. • Ray-Tracing algorithm is inaccurate and severely compromises target coverage. • Recalculated near-maximum dose to OAR generally do not exceed planning limits. • A higher target dose is associated with superior loco-regional control rate. Owing to its short computation time and simplicity, the Ray-Tracing algorithm (RAT) has long been used to calculate dose distributions for the CyberKnife system. However, it is known that RAT fails to fully account for tissue heterogeneity and is therefore inaccurate in the lung. The aim of this study is to make a dosimetric assessment of 219 non-small cell lung cancer CyberKnife plans by recalculating their dose distributions using an independent Monte Carlo (MC) method. For plans initially calculated by RAT without heterogeneity corrections, target coverage was found to be significantly compromised when considering MC doses. Only 35.4% of plans were found to comply to their prescription doses. If the normal tissue dose limits were respected in the treatment planning dose, the MC recalculated dose did not exceed these limits in over 97% of the plans. Comparison of RAT and recalculated-MC doses confirmed the overestimation of RAT doses observed in previous studies. An inverse correlation between the RAT/MC dose ratio and the target size was also found to be statistically significant (p < 10 - 4 ), consistent with other studies. In addition, the inaccuracy and variability in target coverage incurred from dose calculations using RAT without heterogeneity corrections was demonstrated. On average, no clinically relevant differences were observed between MC-calculated dose-to-water and dose-to-medium for all tissues investigated (⩽ 1%). Patients receiving a dose D 95 % larger than 119 Gy in EQD2 10 (or ≈ 52 Gy in 3 fractions) as recalculated by MC were observed to have significantly superior loco-regional progression-free survival rates (p = 0.02) with a hazard ratio of 3.45 (95%CI: 1.14–10.5). [ABSTRACT FROM AUTHOR]

• MC study showed limitation of correlation coefficients in multi-class classification. • Explanation of why categorical outcome prediction requires special consideration. • MC simulation designed to show shortcoming of surrogate biomarkers in clinical trails. In radiation oncology, Machine Learning classification publications are typically related to two outcome classes, e.g. the presence or absence of distant metastasis. However, multi-class classification problems also have great clinical relevance, e.g., predicting the grade of a treatment complication following lung irradiation. This work comprised two studies aimed at making work in this domain less prone to statistical blindsides. In multi-class classification, AUC is not defined, whereas correlation coefficients are. It may seem like solely quoting the correlation coefficient value (in lieu of the AUC value) is a suitable choice. In the first study, we illustrated using Monte Carlo (MC) models why this choice is misleading. We also considered the special case where the multiple classes are not ordinal, but nominal, and explained why Pearson or Spearman correlation coefficients are not only providing incomplete information but are actually meaningless. The second study concerned surrogate biomarkers for a clinical endpoint, which have purported benefits including potential for early assessment, being inexpensive, and being non-invasive. Using a MC experiment, we showed how conclusions derived from surrogate markers can be misleading. The simulated endpoint was radiation toxicity (scale of 0–5). The surrogate marker was the true toxicity grade plus a noise term. Five patient cohorts were simulated, including one control. Two of the cohorts were designed to have a statistically significant difference in toxicity. Under 1000 repeated experiments using the biomarker, these two cohorts were often found to be statistically indistinguishable, with the fraction of such occurrences rising with the level of noise. [ABSTRACT FROM AUTHOR]

• Model validated on 50 patients receiving 60 Gy to prostate and 44 Gy to pelvic nodes. • Model plans had improved sparing of organs-at-risk compared to clinical plans. • Model offers unbiased way to check benefit of different treatment arc configurations. • Model failed to produce reliable DVH predictions for prostate-only treatment plans. To demonstrate the strength of an innovative knowledge-based model-building method for radiotherapy planning using hypofractionated, multi-target prostate patients. An initial RapidPlan model was trained using 48 patients who received 60 Gy to prostate (PTV60) and 44 Gy to pelvic nodes (PTV44) in 20 fractions. To improve the model's goodness-of-fit, an intermediate model was generated using the dose-volume histograms of best-spared organs-at-risk (OARs) of the initial model. Using the intermediate model and manual tweaking, all 48 cases were re-planned. The final model, trained using these re-plans, was validated on 50 additional patients. The validated final model was used to determine any planning advantage of using three arcs instead of two on 16 VMAT cases and tested on 25 additional cases to determine efficacy for single-PTV (PTV60-only) treatment planning. For model validation, PTV V 95% of 99.9% was obtained by both clinical and knowledge-based planning. D 1% was lower for model plans: by 1.23 Gy (PTV60, CI = [1.00, 1.45]), and by 2.44 Gy (PTV44, CI = [1.72, 3.16]). OAR sparing was superior for knowledge-based planning: Δ D mean = 3.70 Gy (bladder, CI = [2.83, 4.57]), and 3.22 Gy (rectum, CI = [2.48, 3.95]); Δ D 2% = 1.17 Gy (bowel bag, CI = [0.64, 1.69]), and 4.78 Gy (femoral heads, CI = [3.90, 5.66]). Using three arcs instead of two, improvements in OAR sparing and PTV coverage were statistically significant, but of magnitudes < 1 Gy. The model failed at reliable DVH predictions for single PTV plans. Our knowledge-based model delivers efficient, consistent plans with excellent PTV coverage and improved OAR sparing compared to clinical plans. [ABSTRACT FROM AUTHOR]

• The GATE MC toolkit was used to model and validate the multislice helical GE BrightSpeed Elite CT model. • An organ dose database for individuals (2.1–14 years age range), undergoing CT examinations was created. • Dependency of absorbed dose and the anatomical characteristics was researched for several organs. • Effective doses-normalized-to-DLP were estimated and correlated with the total body weight. The purpose of this study is to create an organ dose database for pediatric individuals undergoing chest, abdomen/pelvis, and head computed tomography (CT) examinations, and to report the differences in absorbed organ doses, when anatomical differences exist for pediatric patients. The GATE Monte Carlo (MC) toolkit was used to model the GE BrightSpeed Elite CT model. The simulated scanner model was validated with the standard Computed Tomography Dose Index (CTDI) head phantom. Twelve computational models (2.1–14 years old) were used. First, contributions to effective dose and absorbed doses per CTDI vol and per 100 mAs were estimated for all organs. Then, doses per CTDI vol were correlated with patient model weight for the organs inside the scan range for chest and abdomen/pelvis protocols. Finally, effective doses per dose-length product (DLP) were estimated and compared with the conventional conversion k-factors. The system was validated against experimental CTDI w measurements. The doses per CTDI vol and per 100 mAs for selected organs were estimated. The magnitude of the dependency between the dose and the anatomical characteristics was calculated with the coefficient of determination at 0.5–0.7 for the internal scan organs for chest and abdomen/pelvis protocols. Finally, effective doses per DLP were compared with already published data, showing discrepancies between 13 and 29% and were correlated strongly with the total weight (R2 > 0.8) for the chest and abdomen protocols. Big differences in absorbed doses are reported even for patients of similar age or same gender, when anatomical differences exist on internal organs of the body. [ABSTRACT FROM AUTHOR]

• Dose measurements around 50 kVp electronic brachytherapy source. • Radiochromic film linear response function. • Impact of beam hardening effect around 50 kVp sources. We investigate the effect of the GafChromic™ film EBT3 model absorbed dose energy response when used for dose measurements around low-energy photon sources. Monte Carlo based correction procedure in synergy with appropriate calibration curves was shown to provide more accurate absorbed dose (either relative or absolute). An assessment was made of possible dose errors that might be encountered if such energy dependent response is ignored. We measured PDDs in water from a Xoft 50 kVp source using EBT3 film, and compared to PDD measurements acquired with a PTW-TN34013 parallel-plate ionization chamber. For the x-ray source, we simulated spectra using the EGSnrc (BEAMnrc) Monte Carlo code, and calculated Half Value Layer (HVL) at different distances from the source in water. Measurement strips of EBT3 film were positioned at distances of 2–6 cm from the Xoft source in a water phantom using a custom-made holder and irradiated simultaneously. Our results show that film calibration curves obtained at beam qualities near the effective energy of the Xoft 50 kVp source in water lead to variation in absorbed dose energy dependence of the response of around 5%. However, if the calibration curve was established in an MV beam quality, the error in absorbed dose could be as large as 20%. Accurate dose measurements using radiochromic films at low photon energies require that the radiochromic film dosimetry system be calibrated at appropriate corresponding low energies, as large absorbed dose errors are expected when film calibration is performed in MV beam qualities. [ABSTRACT FROM AUTHOR]

• Radiochromic film CTDI measurements using film strips within modified CTDI phantom. • Impact of beam quality changes within CTDI phantom on radiochromic film dosimetry. • Monte Carlo simulated diagnostic radiology beam spectra within CTDI phantom. In this work we use Monte Carlo simulations to investigate change in Computed tomography (CT) X-ray energy spectra between exposures in air and within CT dose index (CTDI) phantom. While the results of these simulations will be relevant when measuring CTDI with any dosimeter, we apply the appropriate beam quality change correction for CTDI measurements using XR-QA2 model GafChromic™ film. Dose profiles were measured with film strips, sandwiched between acrylic rods cut in half, placed within CTDI phantoms and scanned before and after irradiation with document scanner in reflective mode. Reference dosimetry system was calibrated in terms of air kerma in air, which was converted into absorbed dose using ratio of mass-energy absorption coefficients water-to-air for a given beam quality, following the AAPM TG-61 protocol. Beam qualities for all film positions within CTDI phantom show beam softening for HVLs above 6 mm Al and beam hardening for HVLs bellow 6 mm Al. Calculated CTDI values using HVL in air for all CTDI positions, and those calculated using the appropriate calibration curves based on beam quality correction show for Head CTDI phantom differences ranging from 0.3% to 2.1% and for Body CTDI phantom from 2.5% to 5.7%. We describe method for CTDI measurements using radiochromic film dosimetry protocol corrected by the beam quality change within the phantom. Our results show differences in CTDI measurements of up to 5.7% when compared to using film calibration curves for beam quality in air. [ABSTRACT FROM AUTHOR]

Purpose We compare image quality parameters derived from phantom images taken on three commercially available radiotherapy CT simulators. To make an unbiased evaluation, we assured images were obtained with the same surface dose measured using XR-QA2 model GafChromic™ film placed at the imaging phantom surface for all three CT-simulators. Methods Radiotherapy CT simulators GE LS 16, Philips Brilliance Big Bore, and Toshiba Aquilion LB were compared in terms of spatial resolution, low contrast detectability, image uniformity, and contrast to noise ratio using CATPHAN-504 phantom, scanned with Head and Pelvis protocols. Dose was measured at phantom surface, with CT scans repeated until doses on all scanners were within 2%. Results In terms of spatial resolution, the GE simulator appears slightly better, while Philips CT images are superior in terms of SNR for both scanning protocols. The CNR results show that Philips CT images appear to be better, except for high Z material, while Toshiba appears to fit in between the two simulators. Conclusions While the image quality parameters for three RT CT simulators show comparable results, the scanner bore size is of vital importance in various radiotherapy applications. Since the image quality is a function of a large number of confounding parameters, any loss in image quality due to scanner bore size could be compensated by the appropriate choice of scanning parameters, including the exposure and by balancing between the additional imaging dose to the patient and high image quality required in highly conformal RT techniques. [ABSTRACT FROM AUTHOR]

In this work, the response of Farmer-type ionization chambers fitted with high atomic number (Z) walls is studied, and results of the effects of such walls on polarity and ion recombination correction factors in both continuous and pulsed beams are presented. Measurements were made in a continuous Co-60 beam and a pulsed 6 MV linac beam using an Exradin-A12 ionization chamber fitted with the manufacturer's C-552 plastic wall, as well as geometrically identical walls made from aluminum, copper and molybdenum. The bias voltage was changed between 10 values (range: +50 to +560 V). Ion recombination was determined from Jaffé plots and by using the "two-voltage technique". The saturation charge measured with each chamber wall was extrapolated from Jaffé plots. Additionally, the effect of different wall materials on chamber response was studied using MCNP simulations. Results showed that the polarity correction factor is not significantly affected by changes in chamber wall material (within 0.1%). Furthermore, although the saturation charges greatly vary with each chamber wall material, and charge multiplication increases for higher atomic number wall materials, the standard methods of calculating ion recombination yielded results that differed by only 0.2%. Therefore, polarity and ion recombination correction factors are not greatly affected by the chamber wall material. The experimental saturation charges for all the different wall materials agreed well within the uncertainty with MCNP simulations. The breakdown of the linear relationship in Jaffé plots that was previously reported to exist for conventional chamber walls was also observed with the different wall materials. [ABSTRACT FROM AUTHOR]

• G-value was simulated with varying incoming electron energies and phantom sizes. • G-value of hydrated electrons decreases with increasing cluster size and LET. • GEANT4-DNA G-value simulations can be used for clinically relevant energies. In hydrated electron (e− aq) dosimetry, absorbed radiation dose to water is measured by monitoring the concentration of radiation-induced e− aq. However, to obtain accurate dose, the radiation chemical yield of e− aq , G(e− aq) , is needed for the radiation quality/setup under investigation. The aim of this study was to investigate the time-evolution of the G-values for the main generated reactive species during water radiolysis using GEANT4-DNA. The effects of cluster size and linear energy transfer (LET) on G(e− aq) were examined. Validity of GEANT4-DNA for calculation of G(e− aq) for clinically relevant energies was studied. Three scenarios were investigated with different phantom sizes and incoming electron energies (1 keV to 1 MeV). The time evolution of G(e− aq) was in good agreement with published data and did not change with decreasing phantom size. The time-evolution of the G-values increases with increasing LET for all radiolytic species. The particle tracks formed with high-energy electrons are separated and the resulting reactive species develop independently in time. With decreasing energy, the mean separation distance between reactive species decreases. The particle tracks might not initially overlap but will overlap shortly thereafter due to diffusion of reactive species, increasing the probability of e− aq recombination with other species. This also explains the decrease of G(e− aq) with cluster size and LET. Finally, if all factors are kept constant, as the incoming electron energy increases to clinically relevant energies, G(e− aq) remains similar to its value at 1 MeV, hence GEANT4-DNA can be used for clinically relevant energies. [ABSTRACT FROM AUTHOR]

Purpose Radiochromic films change their color upon irradiation due to polymerization of the sensitive component embedded within the sensitive layer. However, agents, other than monitored radiation, can lead to a change in the color of the sensitive layer (temperature, humidity, UV light) that can be considered as a background signal and can be removed from the actual measurement by using a control film piece. In this work, we investigate the impact of the use of control film pieces on both accuracy and uncertainty of dose measured using radiochromic film based reference dosimetry protocol. Methods We irradiated “control” film pieces (EBT3 GafChromic TM film model) to known doses in a range of 0.05–1 Gy, and five film pieces of the same size to 2, 5, 10, 15 and 20 Gy, considered to be “unknown” doses. Depending on a dose range, two approaches to incorporating control film piece were investigated: signal and dose corrected method. Results For dose values greater than 10 Gy, the increase in accuracy of 3% led to uncertainty loss of 5% by using dose corrected approach. At lower doses and signals of the order of 5%, we observed an increase in accuracy of 10% with a loss of uncertainty lower than 1% by using the corrected signal approach. Conclusions Incorporation of the signal registered by the control film piece into dose measurement analysis should be a judgment call of the user based on a tradeoff between deemed accuracy and acceptable uncertainty for a given dose measurement. [ABSTRACT FROM AUTHOR]

Medical physics, both as a scientific discipline and clinical service, hugely contributed and still contributes to the advances in the radiotherapy of prostate cancer. The traditional translational role in developing and safely implementing new technology and methods for better optimizing, delivering and monitoring the treatment is rapidly expanding to include new fields such as quantitative morphological and functional imaging and the possibility of individually predicting outcome and toxicity. The pivotal position of medical physicists in treatment personalization probably represents the main challenge of current and next years and needs a gradual change of vision and training, without losing the traditional and fundamental role of physicists to guarantee a high quality of the treatment. The current focus issue is intended to cover traditional and new fields of investigation in prostate cancer radiation therapy with the aim to provide up-to-date reference material to medical physicists daily working to cure prostate cancer patients. The papers presented in this focus issue touch upon present and upcoming challenges that need to be met in order to further advance prostate cancer radiation therapy. We suggest that there is a smart future for medical physicists willing to perform research and innovate, while they continue to provide high-quality clinical service. However, physicists are increasingly expected to actively integrate their implicitly translational, flexible and high-level skills within multi-disciplinary teams including many clinical figures (first of all radiation oncologists) as well as scientists from other disciplines. [ABSTRACT FROM AUTHOR]

Electron-impact ionization cross sections for atoms and molecules are essential for the modelling of radiation effects in a wide range of applications. Current state-of-the-art theoretical calculations are based on the distorted-wave Born approximation (DWBA), which provides an improvement in accuracy and validity range over the plane-wave Born approximation (PWBA) by accounting consistently for exchange effects as well as the distortion of the projectile wave functions by the field of the target atom. However, numerical DWBA calculations are elaborate and slow, and tabulated data only exist for integrated cross sections, whereas differential cross sections are also needed in Monte Carlo simulations. The relativistic binary-encounter-dipole (RBED) model combines classical binary-encounter theory with Bethe’s PWBA-based dipole model without the need for any empirical adjustable parameters [1] . The analytical RBED model provides integrated as well as differential cross sections and is much simpler than the DWBA [2] , requiring as input only the binding energy, average kinetic energy, and optical oscillator strength (OOS) for each atomic subshell. Due to the difficulty of obtaining accurate OOSs, simplified models (known as RBEB and RBEQ) which assume a simple functional form for the OOS have also been proposed, and have been employed almost exclusively in studies since then. Here we calculate electron-impact ionization cross sections for a set of atoms spanning the periodic table using the more accurate RBED model, relying on OOSs obtained numerically with self-consistent potentials as described in [3] . Compared to RBEB, we find that the RBED results show better agreement with DWBA data for the K-shell of all atoms and over the entire energy range. The improvement is more pronounced for lower-Z elements, where the agreement between RBED and DWBA is near perfect. For higher shells, there is also better agreement at high energies for all elements, but near the threshold the improvement is less consistent and depends on the specific atomic shells. The disagreements between the RBED and DWBA cross sections near the threshold are due to the interplay between Coulomb and exchange effects, and highlight the limitations of using semi-empirical scaling factors. In the near future we will compile tables of RBED data for biologically-relevant elements, and ultimately implement them in Monte Carlo track-structure codes. [ABSTRACT FROM AUTHOR]

The intraoperative radiotherapy in newly diagnosed glioblastoma multiforme (INTRAGO) clinical trial assesses survival in patients with glioblastoma treated with intraoperative radiation therapy (IORT) using the INTRABEAM. Treatment planning for INTRABEAM relies on vendor-provided in-water depth dose curves obtained according to the TARGeted Intraoperative radioTherapy (TARGIT) dosimetry protocol. However, recent studies have shown discrepancies between the estimated TARGIT and delivered doses. This work evaluates the effect of the choice of dosimetry formalism on organs at risk (OAR) doses. A treatment planning framework for INTRABEAM was developed to retrospectively calculate the IORT dose in 8 INTRAGO patients. These patients received an IORT prescription dose of 20 to 30 Gy in addition to external beam radiation therapy. The IORT dose was obtained using (1) the TARGIT method; (2) the manufacturer's V4.0 method; (3) the C Q method, which uses an ionization chamber Monte Carlo (MC) calculated factor; (4) MC dose-to-water; and (5) MC dose-to-tissue. The IORT dose was converted to 2 Gy fractions equivalent dose. According to the TARGIT method, the OAR dose constraints were respected in all cases. However, the other formalisms estimated a higher mean dose to OARs and revealed 1 case where the constraint for the brain stem was exceeded. The addition of the external beam radiation therapy and TARGIT IORT doses resulted in 10 cases of OARs exceeding the dose constraints. The more accurate MC calculation of dose-to-tissue led to the highest dosimetric differences, with 3, 3, 2, and 2 cases (out of 8) exceeding the dose constraint to the brain stem, optic chiasm, optic nerves, and lenses, respectively. Moreover, the mean cumulative dose to brain stem exceeded its constraint of 66 Gy with the MC dose-to-tissue method, which was not evident with the current INTRAGO clinical practice. The current clinical approach of calculating the IORT dose with the TARGIT method may considerably underestimate doses to nearby OARs. In practice, OAR dose constraints may have been exceeded, as revealed by more accurate methods. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the 15-year impact of a transdisciplinary research training program for graduate students, postdoctoral fellows, and clinical trainees focused on radiation science, entitled Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) with a primary objective to build capacity in radiation research.Methods and Materials: Alumni (n = 128) and mentors (n = 41) who participated in STARS21 between 2003 and 2018 were sent an anonymized online survey designed to evaluate the program. Twelve alumni and 7 mentors also volunteered to participate in semistructured interviews. The transcribed interviews were coded and analyzed using NVivo12-Pro software. Alumni employment and publications were assessed from program records and by web-based search queries.Results: Alumni are located in 11 countries, and nearly 90% are employed in a research-oriented career and continue to publish in radiation medicine- or cancer-related fields. Of those invited, 46 alumni (36%) and 12 mentors (29%) completed the online survey. Approximately 87% of alumni valued interdisciplinary collaboration, and 80% indicated that STARS21 had encouraged them to pursue such collaborations. Alumni emphasized that STARS21 assisted their career development, and the majority of alumni and mentors would recommend STARS21 to other trainees (4.48 and 4.58, respectively; 5 = strongly agree). The time invested in the program was perceived by mentors as worthwhile for the knowledge and skills gained by trainees (4.67; 5 = strongly agree), and 64% of mentors indicated that these benefits were associated with improved trainee research productivity. From the alumni and mentor perspectives, the valuable skills acquired from STARS21 included scientific communication (85% and 83%, respectively) and networking (83% and 92%, respectively).Conclusions: STARS21 is an innovative research training program that promotes interdisciplinary collaboration in radiation medicine research, which is valued by alumni and mentor respondents. Alumni can acquire important skill sets for career development, with a large proportion of alumni currently engaged in radiation research around the world. [ABSTRACT FROM AUTHOR]

• CyberKnife delivers higher dose outside PTV compared to conventional SBRT (VMAT/CRT). • Higher dose outside the PTV is associated with reduced distant metastasis recurrence rates in CyberKnife. • Multivariate analysis revealed that threshold dose was of significant importance in predicting distant metastasis. • CyberKnife was found to provide superior local control than conventional SBRT. Previous literature suggests that the dose proximally outside the PTV could have an impact on the incidence of distant metastasis (DM) after SBRT in stage I NSCLC patients. We investigated this observation (along with local failure) in deliveries made by different treatment modalities: robotic mounted linac SBRT (CyberKnife) vs conventional SBRT (VMAT/CRT). This study included 422 stage I NSCLC patients from 2 institutions who received SBRT: 217 treated conventionally and 205 with CyberKnife. The dose behavior outside the PTV of both sub-cohorts were compared by analyzing the mean dose in continuous shells extending 1, 2, 3, ..., 100 mm from the PTV. Kaplan-Meier analysis was performed between the two sub-cohorts with respect to DM-free survival and local progression-free survival. A multivariable Cox proportional hazards model was fitted to the combined cohort (n = 422) with respect to DM incidence and local failure. The shell-averaged dose fall-off beyond the PTV was found to be significantly more modest in CyberKnife plans than in conventional SBRT plans. In a 30 mm shell around the PTV, the mean dose delivered with CyberKnife (38.1 Gy) is significantly larger than with VMAT/CRT (22.8 Gy, p < 10 - 8 ). For 95% of CyberKnife plans, this region receives a mean dose larger than the 21 Gy threshold dose discovered in our previous study. In contrast, this occurs for only 75% of VMAT/CRT plans. The DM-free survival of the entire CyberKnife cohort is superior to that of the 25% of VMAT/CRT patients receiving less than the threshold dose (VMAT / CRT < 21 Gy ), with a hazard ratio of 5.3 (95% CI: 3.0–9.3, p < 10 - 8 ). The 2 year DM-free survival rates were 87% (95% CI: 81%–91%) and 44% (95% CI: 28%–58%) for CyberKnife and the below-threshold dose conventional cohorts, respectively. A multivariable analysis of the combined cohort resulted in the confirmation that threshold dose was a significant predictor of DM(HR = 0.28, 95% CI: 0.15–0.55, p < 10 - 3 ) when adjusted for other clinical factors. CyberKnife was also found to be superior to the entire VMAT/CRT with respect to local control (HR = 3.44, CI: 1.6–7.3). The 2-year local progression-free survival rates for the CyberKnife cohort and the VMAT/CRT cohort were 96% (95% CI: 92%–98%) and 88% (95% CI: 82%–92%) respectively. In standard-of-care CyberKnife treatments, dose distributions that aid distant control are achieved 95% of the time. Although similar doses could be physically achieved by conventional SBRT, this is not always the case with current prescription practices, resulting in worse DM outcomes for 25% of conventional SBRT patients. Furthermore, CyberKnife was found to provide superior local control compared to VMAT/CRT. [ABSTRACT FROM AUTHOR]

Purpose The Papillon technique using 50-kVp soft X-rays to treat rectal adenocarcinomas was developed and clinically implemented in the 1960s. We describe differences between accurate dosimetry and clinical implementation of this technique that is extending from its very inception to date. Methods and Materials A renaissance of the Papillon technique occurred with two recently introduced 50-kVp systems: Papillon+ by Ariane and a custom-made rectal applicator (consisting of a surface applicator inserted into a proctoscope) by iCAD's Xoft Axxent Electronic Brachytherapy (eBT) System (iCad, Inc., Sunnyvale, CA). In contrast to the initial design, we investigated the impact of introducing a plastic lid, which would provide more reproducible and more accurate dose delivery across the rectal adenocarcinoma patient population. We use both parallel-plate chamber and radiochromic film dosimeters to determine differences in basic dosimetry characteristics (beam half-value layers, outputs, percent depth doses, and profiles) between the Xoft Electronic Brachytherapy rectal applicator system with and without the plastic lid in place. Results Compared to the open-cone applicator, the proposed applicator with the plastic lid produces a slightly harder (more penetrating) beam quality (half-value layer of 1.4 vs. 1.3-mm Al), but with reduced output (by 33%), and a slightly broader beam with flatness not worse than 3% and symmetry not worse than 2%. Conclusions In addition to characterizing beam properties modified by the possible introduction of the plastic cap, we also pointed out and addressed misconceptions in the use of radiochromic films for dose measurements at low-energy photon beams. [ABSTRACT FROM AUTHOR]

Purpose: The presence of multiple serial organs at risk (OARs) in close proximity to the tumor makes treatment planning for glioblastoma (GBM) complex and time consuming. The present study aimed to create a knowledge-based (KB) radiation therapy model for GBM patients using RapidPlan.Methods and Materials: An initial model was trained using 82 glioblastoma patients treated with 60 Gy in 30 fractions. Plans were created using either volumetric modulated arc therapy (VMAT) or intensity modulated radiation therapy (IMRT). To improve the goodness-of-fit of the model, an intermediate model was generated by using the dose-volume histograms (DVHs) of best spared OARs of the initial model. Using the intermediate model and manual refinement, all 82 cases were replanned, resulting in the final model. The final model was validated on an independent set of 45 patients with GBM, astrocytoma, oligodendroglioma, and meningioma.Results: The plans created by the final model exhibited superior planning target volume (PTV) dose metrics compared with manual clinical plans: ΔD99%=-0.52 ± 0.20 Gy, and ΔD1%=0.80 ± 0.13 Gy (differences are computed as clinical-model). OAR maximum doses were statistically similar, with improved optic apparatus sparing (ΔDmax=2.78 ± 0.82 Gy). Stated improvements correspond to P<.05. The KB planning time is typically 7 minutes for IMRT and 13 minutes for VMAT, compared with a typical 4 hours for manual planning.Conclusions: The KB approach results in significant improvement in planning efficiency and in superior PTV coverage and better normal tissue sparing irrespective of tumor size and location within the brain. [ABSTRACT FROM AUTHOR]

Purpose Current high-dose-rate brachytherapy skin treatments with the Freiburg flap (FF) applicator are planned with treatment planning systems based on the American Association of Physicists in Medicine TG-43 data sets, which assume full backscatter conditions in dose calculations. The aim of this work is to describe an experimental method based on radiochromic film dosimetry to evaluate dose calculation accuracy during surface treatments with the FF applicator at different depths and bolus thicknesses. Methods and Materials Absolute doses were measured using a reference EBT3 radiochromic film dosimetry system within a Solid Water phantom at different depths (0, 0.5, 1, 2, and 3 cm) with respect to the phantom surface. The impact of bolus (up to 3-cm thickness) placed on top of the applicator was investigated for two clinical loadings created using Oncentra MasterPlan: 5 cm × 5 cm and 11 cm × 11 cm. Results For smaller loading and depths beyond 2 cm and for larger loading and depths beyond 1 cm, the dose difference was less than 3% (±4%). At shallower depths, differences of up to 6% (±4%) at the surface were observed if no bolus was added. The addition of 2-cm bolus for the smaller loading and 1 cm for larger loading minimized the difference to less than 3% (±4%). Conclusions For typical FF applicator loading sizes, the actual measured dose was 6% (±4%) lower at the skin level when compared with TG-43. Additional bolus above the FF was shown to decrease the dose difference. The consideration of change in clinical practice should be carefully investigated in light of clinical reference data. [ABSTRACT FROM AUTHOR]

There has been significant recent interest in combining radiation therapy and photodynamic therapy for cancer treatment. One proposed method involves conjugating photosensitizers (PS) to scintillating nanoparticles. However, the production of nanoscintillators that are stable in biological media is problematic since many of the commonly used compositions chelate phosphate. In this paper, the problem was solved by first synthesizing LaF 3 nanoparticles, followed by surface modification with alendronate, which serves as a stable anchor for conjugation of molecules of interest. The nanoparticles had an average diameter of 4 nm, and were doped with either Ce 3+ , Tb 3+ , or both. In every case, a LaF 3 shell was added. In subsequent steps, poly(ethylene) glycol (PEG) and photosensitizers (either chlorin e6 or rose bengal) were covalently linked to the alendronate ligand via an amide bond. This new formulation is stable in several solutions and buffers used commonly in the laboratory for cell culture. Moreover, cellular uptake and lack of toxicity up to a concentration of 50 μM were observed in B16 murine melanoma cells. Energy transfer between the doped nanoparticle core and the conjugated photosensitizers was demonstrated using UV excitation, and scintillation was demonstrated using x-rays. [ABSTRACT FROM AUTHOR]

Purpose In the past, film dosimetry was developed into a powerful tool for external beam radiotherapy treatment verification and quality assurance. The objective of this work was the development and clinical testing of the EBT3 model GafChromic film based brachytherapy quality assurance (QA) system. Methods and Materials Retrospective dosimetry study was performed to test a patient-specific QA system for preoperative endorectal brachytherapy that uses a radiochromic film dosimetry system. A dedicated phantom for brachytherapy applicator used for rectal cancer treatment was fabricated enabling us to compare calculated-to-measured dose distributions. Starting from the same criteria used for external beam intensity-modulated radiation therapy QA (3%, 3 mm), passing criteria for high- and low-dose gradient regions were subsequently determined. Finally, we investigated the QA system's sensitivity to controlled source positional errors on selected patient plans. Results In low-dose gradient regions, measured dose distributions with criteria of 3%, 3 mm barely passed the test, as they showed 95% passing pixels. However, in the high-dose gradient region, a more stringent condition could be established. Both criteria of 2%, 3 mm and 3%, 2 mm with gamma function calculated using normalization to the same absolute dose value in both measured and calculated dose distributions, and matrix sizes rescaled to match each other showed more than 95% of pixels passing, on average, for 15 patient plans analyzed. Conclusions Although the necessity of the patient-specific brachytherapy QA needs yet to be justified, we described a radiochromic film dosimetry–based QA system that can be a part of the brachytherapy commissioning process, as well as yearly QA program. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To compare few leaf electron collimator (FLEC)-based modulated electron radiotherapy (MERT) to conventional direct electron (DE) and volumetric modulated photon arc therapy (VMAT) for the treatment of tumour bed boost in breast cancer. Materials and methods: Fourteen patients with breast cancer treated by lumpectomy and requiring post-operative whole breast radiotherapy with tumour bed boost were planned retrospectively using conventional DE, VMAT and FLEC-based MERT. The planning goal was to deliver 10Gy to at least 95% of the tumour bed volume. Dosimetry parameters for all techniques were compared. Results: Dose evaluation volume (DEV) coverage and homogeneity were best for MERT (D 98 =9.77Gy, D 2 =11.03Gy) followed by VMAT (D 98 =9.56Gy, D 2 =11.07Gy) and DE (D 98 =9.81Gy, D 2 =11.52Gy). Relative to the DE plans, the MERT plans predicted a reduction of 35% in mean breast dose (p <0.05), 54% in mean lung dose (p <0.05) and 46% in mean body dose (p <0.05). Relative to the VMAT plans, the MERT plans predicted a reduction of 24%, 36% and 39% in mean breast dose, heart dose and body dose, respectively (p <0.05). Conclusions: MERT plans were a considerable improvement in dosimetry over DE boost plans. There was a dosimetric advantage in using MERT over VMAT for increased DEV conformity and low-dose sparing of healthy tissue including the integral dose; however, the cost is often an increase in the ipsilateral lung high-dose volume. [Copyright &y& Elsevier]

Purpose: To present a new method of evaluating the correlation between radiotherapy (RT)-induced fibrosis and the local dose delivered to non–small-cell lung cancer patients. Methods and Materials: Treatment plans were generated using the CadPlan treatment planning system (pencil beam, no heterogeneity corrections), and RT delivery was based on these plans. Retrospective Monte-Carlo dose calculations were performed, and the Monte-Carlo distributions of dose to real tissue were calculated using the planning computed tomography (CT) images and the number of monitor units actually delivered. After registration of the follow-up CT images with the planning CT images, different grades of radiologic fibrosis were automatically segmented on the follow-up CT images. Subsequently, patient-specific fibrosis probabilities were studied as a function of the local dose and a function of time after RT completion. Results: A strong patient-specific variation in the fibrosis volumes was found during the follow-up period. For both lungs, the threshold dose for which the probability of fibrosis became significant coincided with the threshold dose at which significant volumes of the lung were exposed. At later stages, only fibrosis localized in the high-dose regions persisted for both lungs. Overall, the Monte-Carlo dose distributions correlated much better with the probability of RT-induced fibrosis than did the CadPlan dose distributions. Conclusion: The presented method allows for an accurate, systematic, patient-specific and post-RT time-dependent numeric study of the relationship between RT-induced fibrosis and the local dose. [Copyright &y& Elsevier]