Showing papers on "Dosimetry published in 2020"

Report of AAPM Task Group 235 Radiochromic Film Dosimetry: An Update to TG-55.

Abstract: The use of radiochromic film (RCF) dosimetry in radiation therapy is extensive due to its high level of achievable accuracy for a wide range of dose values and its suitability under a variety of measurement conditions. However, since the publication of the 1998 AAPM Task Group 55, Report No. 63 on RCF dosimetry, the chemistry, composition, and readout systems for RCFs have evolved steadily. There are several challenges in using the new RCFs, readout systems and validation of the results depending on their applications. Accurate RCF dosimetry requires understanding of RCF selection, handling and calibration methods, calibration curves, dose conversion methods, correction methodologies as well as selection, operation and quality assurance (QA) programs of the readout systems. Acquiring this level of knowledge is not straight forward, even for some experienced users. This Task Group report addresses these issues and provides a basic understanding of available RCF models, dosimetric characteristics and properties, advantages and limitations, configurations, and overall elemental compositions of the RCFs that have changed over the past 20 yr. In addition, this report provides specific guidelines for data processing and analysis schemes and correction methodologies for clinical applications in radiation therapy.

AAPM TG 191 Clinical Use of Luminescent Dosimeters: TLDs and OSLDs

Abstract: Thermoluminescent dosimeters (TLD) and optically stimulated luminescent dosimeters (OSLD) are practical, accurate, and precise tools for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescence dosimetry in a clinical setting. This includes: (a) to review the variety of TLD/OSLD materials available, including features and limitations of each; (b) to outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used; (c) to develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice; and (d) to develop guidelines for special medically relevant uses of TLDs/OSLDs such as mixed photon/neutron field dosimetry, particle beam dosimetry, and skin dosimetry. While this report provides general guidelines for TLD and OSLD processes, the report provides specific details for TLD-100 and nanoDotTM dosimeters because of their prevalence in clinical practice.

Radiological parameters of bismuth oxide glasses using the Phy-X/PSD software

Abstract: Radiation physics and dosimetry have recently been very popular in physics due to their extended utilizations in different scientific studies. This is important for radiation protection issues, par...

Dosimetry for FLASH Radiotherapy: A Review of Tools and the Role of Radioluminescence and Cherenkov Emission

Abstract: While spatial dose conformity delivered to a target volume has been pushed to its practical limits with advanced treatment planning and delivery, investigations in novel temporal dose delivery are unfolding new mechanisms. Recent advances in ultra-high dose radiotherapy, abbreviated as FLASH, indicate the potential for reduction in healthy tissue damage while preserving tumor control. FLASH therapy relies on very high dose rate of > 40Gy/sec with sub-second temporal beam modulation, taking a seemingly opposite direction from the conventional paradigm of fractionated therapy. FLASH brings unique challenges to dosimetry, beam control, and verification, as well as complexity of radiobiological effective dose through altered tissue response. In this review, we compare the dosimetric methods capable of operating under high dose rate environments. Due to excellent dose-rate independence, superior spatial (~<1 mm) and temporal (~ns) resolution achievable with Cherenkov and scintillation-based detectors, we show that luminescent detectors have a key role to play in the development of FLASH-RT, as the field rapidly progresses towards clinical adaptation. Additionally, we show that the unique ability of certain luminescence-based methods to provide tumor oxygenation maps in real-time with submillimeter resolution can elucidate the radiobiological mechanisms behind the FLASH effect. In particular, such techniques will be crucial for understanding the role of oxygen in mediating the FLASH effect.

First measurements of the radiation dose on the lunar surface

Abstract: Human exploration of the Moon is associated with substantial risks to astronauts from space radiation. On the surface of the Moon, this consists of the chronic exposure to galactic cosmic rays and sporadic solar particle events. The interaction of this radiation field with the lunar soil leads to a third component that consists of neutral particles, i.e., neutrons and gamma radiation. The Lunar Lander Neutrons and Dosimetry experiment aboard China’s Chang’E 4 lander has made the first ever measurements of the radiation exposure to both charged and neutral particles on the lunar surface. We measured an average total absorbed dose rate in silicon of 13.2 ± 1 μGy/hour and a neutral particle dose rate of 3.1 ± 0.5 μGy/hour.

The challenge of ionisation chamber dosimetry in ultra-short pulsed high dose-rate Very High Energy Electron beams

Abstract: High dose-rate radiotherapy, known as FLASH, has been shown to increase the differential response between healthy and tumour tissue. Moreover, Very High Energy Electrons (VHEEs) provide more favourable dose distributions than conventional radiotherapy electron and photon beams. Plane-parallel ionisation chambers are the recommended secondary standard systems for clinical reference dosimetry of electrons, therefore chamber response to these high energy and high dose-per-pulse beams must be well understood. Graphite calorimetry, the UK primary standard, has been employed to measure the dose delivered from a 200 MeV pulsed electron beam. This was compared to the charge measurements of a plane-parallel ionisation chamber to determine the absolute collection efficiency and infer the ion recombination factor. The dose-per-pulse measured by the calorimeter ranged between 0.03 Gy/pulse and 5.26 Gy/pulse, corresponding to collection efficiencies between 97% and 4%, respectively. Multiple recombination models currently available have been compared with experimental results. This work is directly applicable to the development of standard dosimetry protocols for VHEE radiotherapy, FLASH radiotherapy and other high dose-rate modalities. However, the use of secondary standard ionisation chambers for the dosimetry of high dose-per-pulse VHEEs has been shown to require large corrections for charge collection inefficiency.

The superior predictive value of 166Ho-scout compared with 99mTc-macroaggregated albumin prior to 166Ho-microspheres radioembolization in patients with liver metastases.

Abstract: As an alternative to technetium-99m-macroaggregated albumin (99mTc-MAA), a scout dose of holmium-166 (166Ho) microspheres can be used prior to 166Ho-radioembolization. The use of identical particles for pre-treatment and treatment procedures may improve the predictive value of pre-treatment analysis of distribution. The aim of this study was to analyze the agreement between 166Ho-scout and 166Ho-therapeutic dose in comparison with the agreement between 99mTc-MAA and 166Ho-therapeutic dose. Two separate scout dose procedures were performed (99mTc-MAA and 166Ho-scout) before treatment in 53 patients. First, qualitative assessment was performed by two blinded nuclear medicine physicians who visually rated the agreement between the 99mTc-MAA, 166Ho-scout, and 166Ho-therapeutic dose SPECT-scans (i.e., all performed in the same patient) on a 5-point scale. Second, agreement was measured quantitatively by delineating lesions and normal liver on FDG-PET/CT. These volumes of interest (VOIs) were co-registered to the SPECT/CT images. The predicted absorbed doses (based on 99mTc-MAA and 166Ho-scout) were compared with the actual absorbed dose on post-treatment SPECT. A total of 23 procedures (71 lesions, 22 patients) were included for analysis. In the qualitative analysis, 166Ho-scout was superior with a median score of 4 vs. 2.5 for 99mTc-MAA (p < 0.001). The quantitative analysis showed significantly narrower 95%-limits of agreement for 166Ho-scout in comparison with 99mTc-MAA when evaluating lesion absorbed dose (− 90.3 and 105.3 Gy vs. − 164.1 and 197.0 Gy, respectively). Evaluation of normal liver absorbed dose did not show difference in agreement between both scout doses and 166Ho-therapeutic dose (− 2.9 and 5.5 Gy vs − 3.6 and 4.1 Gy for 99mTc-MAA and 166Ho-scout, respectively). In this study, 166Ho-scout was shown to have a superior predictive value for intrahepatic distribution in comparison with 99mTc-MAA.

A Dose of Reality: How 20 Years of Incomplete Physics and Dosimetry Reporting in Radiobiology Studies May Have Contributed to the Reproducibility Crisis.

Abstract: Purpose A large proportion of preclinical or translational studies using radiation have poor replicability. For a study involving radiation exposure to be replicable, interpretable, and comparable, its experimental methodology must be well reported, particularly in terms of irradiation protocol, including the amount, rate, quality, and geometry of radiation delivery. Here we perform the first large-scale literature review of the current state of reporting of essential experimental physics and dosimetry details in the scientific literature. Methods and Materials For 1758 peer-reviewed articles from 469 journals, we evaluated the reporting of basic experimental physics and dosimetry details recommended by the authoritative National Institute of Standards and Technology symposium. Results We demonstrate that although some physics and dosimetry parameters, such as dose, source type, and energy, are well reported, the majority are not. Furthermore, highly cited journals and articles are systematically more likely to be lacking experimental details related to the irradiation protocol. Conclusions These findings show a crucial deficiency in the reporting of basic experimental details and severely affect the reproducibility and translatability of a large proportion of radiation biology studies.

Radiation Dosimetry in 177Lu-PSMA-617 Therapy Using a Single Posttreatment SPECT/CT Scan: A Novel Methodology to Generate Time- and Tissue-Specific Dose Factors.

Abstract: Calculation of radiation dosimetry in targeted nuclear medicine therapies is traditionally resource-intensive, requiring multiple posttherapy SPECT acquisitions. An alternative approach is to take advantage of existing pharmacokinetic data from these smaller cohorts to enable dose computation from a single posttreatment scan in a manner that may be applied to a much broader patient population. Methods: In this work, a technical description of simplified dose estimation is presented and applied to the assessment of 177Lu-prostate-specific membrane antigen (PSMA)-617 therapy for metastatic prostate cancer. By normalizing existing time-activity curves to a single measurement time, it is possible to calculate a mean and range of time-integrated activity values that relate to absorbed radiation dose. To assist with accurate pharmacokinetic modeling of the training cohort, a method for contour-guided image registration was developed. Results: Tissue-specific dose conversion factors for common posttreatment imaging times are reported along with a characterization of added uncertainty in comparison to a traditional serial imaging protocol. Single-time-point dose factors for tumor were determined to be 11.0, 12.1, 13.6, and 15.2 Gy per MBq/mL at image times of 24, 48, 72, and 96 h, respectively. For normal tissues, parotid gland factors were 6.7, 9.4, 13.3, and 19.3 Gy per MBq/mL at those times, and kidneys were 7.1, 10.3, 15.0, and 22.0 Gy per MBq/mL. Tumor dose estimates were most accurate using delayed scanning at times beyond 72 h. Dose to healthy tissues is best characterized by scanning patients in the first 2 d of treatment because of the larger degree of tracer clearance in this early phase. Conclusion: This work demonstrates a means for efficient dose estimation in 177Lu-PSMA-617 therapy. By providing methods to simplify and potentially automate radiation dosimetry, we hope to accelerate the understanding of radiobiology and development of dose-response models in this unique therapeutic context.

A deep learning approach to radiation dose estimation.

Abstract: Purpose: Currently methods for predicting absorbed dose after administering a radiopharmaceutical are rather crude in daily clinical practice. Most importantly individual tissue density distributions as well as local variations of the concentration of the radiopharmaceutical are commonly neglected. The current study proposes machine learning techniques like Green's function-based empirical mode decomposition and deep learning methods on U-net architectures in conjunction with soft tissue kernel Monte Carlo (MC) simulations to overcome current limitations in precision and reliability of dose estimations for clinical dosimetric applications. Methods: We present a hybrid method (DNN-EMD) based on deep neural networks (DNN) in combination with empirical mode decomposition (EMD) techniques. The algorithm receives Computed Tomography (CT) tissue density maps and dose maps, estimated according to the MIRD protocol, i.e., employing whole organ S-values and related time-integrated activities (TIAs), and from measured SPECT distributions of 177-Lu radionuclei, and learns to predict individual absorbed dose distributions. Density maps are replaced by their intrinsic modes as deduced from an EMD analysis. The system is trained using individual full MC simulations as reference. Results: Data from a patient cohort of 26 subjects are reported in this study. The proposed methods were validated employing a leave-one-out cross-validation technique. Deviations of estimated dose from corresponding MC results corroborate a superior performance of the newly proposed hybrid DNN-EMD method compared to its related MIRD DVK dose calculation. Not only are the mean deviations much smaller with the new method, but also the related variances are much reduced. If intrinsic modes of the tissue density maps are input to the algorithm, variances become even further reduced though the mean deviations are less affected. Conclusion: The newly proposed hybrid DNN-EMD method for individualized radiation dose prediction outperforms the MIRD DVK dose calculation method. It is fast enough to be of use in daily clinical practice.

FLASH Investigations Using Protons: Design of Delivery System, Preclinical Setup and Confirmation of FLASH Effect with Protons in Animal Systems

Abstract: Extremely high-dose-rate irradiation, referred to as FLASH, has been shown to be less damaging to normal tissues than the same dose administrated at conventional dose rates. These results, typically seen at dose rates exceeding 40 Gy/s (or 2,400 Gy/min), have been widely reported in studies utilizing photon or electron radiation as well as in some proton radiation studies. Here, we report the development of a proton irradiation platform in a clinical proton facility and the dosimetry methods developed. The target is placed in the entry plateau region of a proton beam with a specifically designed double-scattering system. The energy after the double-scattering system is 227.5 MeV for protons that pass through only the first scatterer, and 225.5 MeV for those that also pass through the second scatterer. The double-scattering system was optimized to deliver a homogeneous dose distribution to a field size as large as possible while keeping the dose rate >100 Gy/s and not exceeding a cyclotron current of 300 nA. We were able to obtain a collimated pencil beam (1.6 × 1.2 cm2 ellipse) at a dose rate of ∼120 Gy/s. This beam was used for dose-response studies of partial abdominal irradiation of mice. First results indicate a potential tissue-sparing effect of FLASH.

Radioembolization of hepatocarcinoma with 90 Y glass microspheres: treatment optimization using the dose-toxicity relationship

Abstract: Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/< 1.1 mg/dL. These results are valid for a 90Y glass microsphere administration 4 days after the reference time. Given the low predictive accuracy of 99mTc-MAA on lesion absorbed dose reported by several authors, an optimized TARE with 90Y glass microspheres with lobar injection 4 days after reference time should aim at an absorbed dose averaged over the whole non-tumoural liver of 50 Gy/90 Gy for basal bilirubin higher/lower than 1.1 mg/dL, respectively.

EANM Dosimetry Committee series on standard operational procedures for internal dosimetry for 131 I mIBG treatment of neuroendocrine tumours

Abstract: The purpose of the EANM Dosimetry Committee Series on “Standard Operational Procedures for Dosimetry” (SOP) is to provide advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This SOP describes image and data acquisition parameters and dosimetry calculations to determine the absorbed doses delivered to whole-body, tumour and normal organs following a therapeutic administration of 131I mIBG for the treatment of neuroblastoma or adult neuroendocrine tumours. Recommendations are based on evidence in recent literature where available and on expert opinion within the community. This SOP is intended to promote standardisation of practice within the community and as such is based on the facilities and expertise that should be available to any centre able to perform specialised treatments with radiopharmaceuticals and patient-specific dosimetry. A clinical example is given to demonstrate the application of the absorbed dose calculations.

Validation of linear energy transfer computed in a Monte Carlo dose engine of a commercial treatment planning system

Abstract: The relative biological effectiveness (RBE) of protons is highly variable and difficult to quantify. However, RBE is related to the local ionization density, which can be related to the physical measurable dose weighted linear energy transfer (LETD). The aim of this study was to validate the LETD calculations for proton therapy beams implemented in a commercially available treatment planning system (TPS) using microdosimetry measurements and independent LETD calculations (Open-MCsquare (MCS)). The TPS (RayStation v6R) was used to generate treatment plans on the CIRS-731-HN anthropomorphic phantom for three anatomical sites (brain, nasopharynx, neck) for a spherical target (O = 5 cm) with uniform target dose to calculate the LETD distribution. Measurements were performed at the University Medical Center Groningen proton therapy center (Proteus Plus, IBA) using a µ +-probe utilizing silicon on insulator microdosimeters capable of detecting lineal energies as low as 0.15 keV µm-1 in tissue. Dose averaged mean lineal energy [Formula: see text] depth-profiles were measured for 70 and 130 MeV spots in water and for the three treatment plans in water and an anthropomorphic phantom. The [Formula: see text] measurements were compared to the LETD calculated in the TPS and MCS independent dose calculation engine. D · [Formula: see text] was compared to D · LETD in terms of a gamma-index with a distance-to-agreement criteria of 2 mm and increasing dose difference criteria to determine the criteria for which a 90% pass rate was accomplished. Measurements of D · [Formula: see text] were in good agreement with the D · LETD calculated in the TPS and MCS. The 90% passing rate threshold was reached at different D · LETD difference criteria for single spots (TPS: 1% MCS: 1%), treatment plans in water (TPS: 3% MCS: 6%) and treatment plans in an anthropomorphic phantom (TPS: 6% MCS: 1%). We conclude that D · LETD calculations accuracy in the RayStation TPS and open MCSquare are within 6%, and sufficient for clinical D · LETD evaluation and optimization. These findings remove an important obstacle in the road towards clinical implementation of D · LETD evaluation and optimization of proton therapy treatment plans. Novelty and significance The dose weighed linear energy transfer (LETD) distribution can be calculated for proton therapy treatment plans by Monte Carlo dose engines. The relative biological effectiveness (RBE) of protons is known to vary with the LETD distribution. Therefore, there exists a need for accurate calculation of clinical LETD distributions. Previous LETD validations have focused on general purpose Monte Carlo dose engines which are typically not used clinically. We present the first validation of mean lineal energy [Formula: see text] measurements of the LETD against calculations by the Monte Carlo dose engines of the Raystation treatment planning system and open MCSquare.

Technical advances in x-ray microbeam radiation therapy.

Abstract: In the last 25 years microbeam radiation therapy (MRT) has emerged as a promising alternative to conventional radiation therapy at large, third generation synchrotrons. In MRT, a multi-slit collimator modulates a kilovoltage x-ray beam on a micrometer scale, creating peak dose areas with unconventionally high doses of several hundred Grays separated by low dose valley regions, where the dose remains well below the tissue tolerance level. Pre-clinical evidence demonstrates that such beam geometries lead to substantially reduced damage to normal tissue at equal tumour control rates and hence drastically increase the therapeutic window. Although the mechanisms behind MRT are still to be elucidated, previous studies indicate that immune response, tumour microenvironment, and the microvasculature may play a crucial role. Beyond tumour therapy, MRT has also been suggested as a microsurgical tool in neurological disorders and as a primer for drug delivery. The physical properties of MRT demand innovative medical physics and engineering solutions for safe treatment delivery. This article reviews technical developments in MRT and discusses existing solutions for dosimetric validation, reliable treatment planning and safety. Instrumentation at synchrotron facilities, including beam production, collimators and patient positioning systems, is also discussed. Specific solutions reviewed in this article include: dosimetry techniques that can cope with high spatial resolution, low photon energies and extremely high dose rates of up to 15 000 Gy s-1, dose calculation algorithms-apart from pure Monte Carlo Simulations-to overcome the challenge of small voxel sizes and a wide dynamic dose-range, and the use of dose-enhancing nanoparticles to combat the limited penetrability of a kilovoltage energy spectrum. Finally, concepts for alternative compact microbeam sources are presented, such as inverse Compton scattering set-ups and carbon nanotube x-ray tubes, that may facilitate the transfer of MRT into a hospital-based clinical environment. Intensive research in recent years has resulted in practical solutions to most of the technical challenges in MRT. Treatment planning, dosimetry and patient safety systems at synchrotrons have matured to a point that first veterinary and clinical studies in MRT are within reach. Should these studies confirm the promising results of pre-clinical studies, the authors are confident that MRT will become an effective new radiotherapy option for certain patients.

Dosimetric comparison of fractionated radiosurgery plans using frameless Gamma Knife ICON and CyberKnife systems with linear accelerator-based radiosurgery plans for multiple large brain metastases.

Abstract: Objective For patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues. Methods Ten patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42-49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21-30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases. Results Plans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans. Conclusions All 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.

Personalised Dosimetry in Radioembolisation for HCC: Impact on Clinical Outcome and on Trial Design.

Abstract: Selective internal radiation therapy (SIRT) of hepatocellular carcinoma (HCC) has been used for many years, usually without any specific dosimetry endpoint. Despite good clinical results in early phase studies or in cohort studies, three randomized trials in locally advanced HCC available failed to demonstrate any improvement of overall overall survival (OS) in comparison with sorafenib. In recent years, many studies have evaluated the dosimetry of SIRT using either a simulation-based dosimetry (macroaggregated albumin (MAA)-based) or a post-therapy-based one (90Y-based). The goal of this review is to present the dosimetry concept, tools available, its limitations, and main clinical results described for HCC patients treated with 90Y-loaded resin or glass microspheres. With MAA-based dosimetry, the threshold tumor doses allowing for a response were between 100 and 210 Gy for resin microspheres and between 205 and 257 Gy for glass microspheres. The significant impact of the tumor dose on OS was reported with both devices. The correlation between 90Y-based dosimetry and response was also reported. Regarding the safety, preliminary results are available for both products but with a larger range of normal liver doses values correlated with liver toxicities due to numerous confounding factors. Based on those results, international expert group recommendations for personalized dosimetry have been provided for both devices. The clinical impact of personalized dosimetry has been recently confirmed in a multicenter randomized study demonstrating a doubling of the response rate and an OS of 150% while using personalized dosimetry. Even if technical dosimetry improvements are still under investigation, the use of personalized dosimetry has to be generalized for both clinical practice and trial design.

Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group.

Abstract: The limits of radiation tolerance, which often deter the use of large doses, have been a major challenge to the treatment of bulky primary and metastatic cancers. A novel technique using spatial modulation of megavoltage therapy beams, commonly referred to as spatially fractionated radiation therapy (SFRT) (e.g., GRID radiation therapy), which purposefully maintains a high degree of dose heterogeneity across the treated tumor volume, has shown promise in clinical studies as a method to improve treatment response of advanced, bulky tumors. Compared to conventional uniform-dose radiotherapy, the complexities of megavoltage GRID therapy include its highly heterogeneous dose distribution, very high prescription doses, and the overall lack of experience among physicists and clinicians. Since only a few centers have used GRID radiation therapy in the clinic, wide and effective use of this technique has been hindered. To date, the mechanisms underlying the observed high tumor response and low toxicity are still not well understood. To advance SFRT technology and planning, the Physics Working Group of the Radiosurgery Society (RSS) GRID/Lattice, Microbeam and Flash Radiotherapy Working Groups, was established after an RSS-NCI Workshop. One of the goals of the Physics Working Group was to develop consensus recommendations to standardize dose prescription, treatment planning approach, response modeling and dose reporting in GRID therapy. The objective of this report is to present the results of the Physics Working Group's consensus that includes recommendations on GRID therapy as an SFRT technology, field dosimetric properties, techniques for generating GRID fields, the GRID therapy planning methods, documentation metrics and clinical practice recommendations. Such understanding is essential for clinical patient care, effective comparisons of outcome results, and for the design of rigorous clinical trials in the area of SFRT. The results of well-conducted GRID radiation therapy studies have the potential to advance the clinical management of bulky and advanced tumors by providing improved treatment response, and to further develop our current radiobiology models and parameters of radiation therapy design.

FFF-VMAT for SBRT of lung lesions: Improves dose coverage at tumor-lung interface compared to flattened beams.

Abstract: Purpose To quantify the differences in dosimetry as a function of ipsilateral lung density and treatment delivery parameters for stereotactic, single dose of volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) delivered with 6X flattening filter free (6X-FFF) beams compared to traditional flattened 6X (6X-FF) beams. Materials/methods Thirteen consecutive early stage I-II non-small-cell-lung cancer (NSCLC) patients were treated with highly conformal noncoplanar VMAT SBRT plans (3-6 partial arcs) using 6X-FFF beam and advanced Acuros-based dose calculations to a prescription dose of 30 Gy in one fraction to the tumor margin. These clinical cases included relatively smaller tumor (island tumors) sizes (2.0-4.2 cm diameters) and varying average ipsilateral lung densities between 0.14 g/cc and 0.34 g/cc. Treatment plans were reoptimized with 6X-FF beams for identical beam/arc geometries and planning objectives. For same target coverage, the organs-at-risk (OAR) dose metrics as a function of ipsilateral lung density were compared between 6X-FFF and 6X-FF plans. Moreover, monitor units (MU), beam modulation factor (MF) and beam-on time (BOT) were evaluated. Results Both plans met the RTOG-0915 protocol compliance. The ipsilateral lung density and the tumor location heavily influenced the treatment plans with 6X-FFF and 6X-FF beams, showing differences up to 12% for the gradient indices. For similar target coverage, 6X-FFF beams showed better target conformity, lower intermediate dose-spillage, and lower dose to the OAR. Additionally, BOT was reduced by a factor of 2.3 with 6X-FFF beams compared to 6X-FF beams. Conclusion While prescribing dose to the tumor periphery, 6X-FFF VMAT plans for stereotactic single-dose lung SBRT provided similar target coverage with better dose conformity, superior intermediate dose-spillage (improved dose coverage at tumor interface), and improved OAR sparing compared to traditional 6X-FF beams and significantly reduced treatment time. The ipsilateral lung density and tumor location considerably affected dose distributions requiring special attention for clinical SBRT plan optimization on a per-patient basis. Clinical follow up of these patients for tumor local-control rate and treatment-related toxicities is in progress.

RapidBrachyDL: Rapid Radiation Dose Calculations in Brachytherapy Via Deep Learning.

Abstract: Purpose Detailed and accurate absorbed dose calculations from radiation interactions with the human body can be obtained with the Monte Carlo (MC) method. However, the MC method can be slow for use in the time-sensitive clinical workflow. The aim of this study was to provide a solution to the accuracy-time trade-off for 192Ir-based high-dose-rate brachytherapy by using deep learning. Methods and Materials RapidBrachyDL, a 3-dimensional deep convolutional neural network (CNN) model, is proposed to predict dose distributions calculated with the MC method given a patient’s computed tomography images, contours of clinical target volume (CTV) and organs at risk, and treatment plan. Sixty-one patients with prostate cancer and 10 patients with cervical cancer were included in this study, with data from 47 patients with prostate cancer being used to train the model. Results Compared with ground truth MC simulations, the predicted dose distributions by RapidBrachyDL showed a consistent shape in the dose-volume histograms (DVHs); comparable DVH dosimetric indices including 0.73% difference for prostate CTV D90, 1.1% for rectum D2cc, 1.45% for urethra D0.1cc, and 1.05% for bladder D2cc; and substantially smaller prediction time, acceleration by a factor of 300. RapidBrachyDL also demonstrated good generalization to cervical data with 1.73%, 2.46%, 1.68%, and 1.74% difference for CTV D90, rectum D2cc, sigmoid D2cc, and bladder D2cc, respectively, which was unseen during the training. Conclusion Deep CNN-based dose estimation is a promising method for patient-specific brachytherapy dosimetry. Desired radiation quantities can be obtained with accuracies arbitrarily close to those of the source MC algorithm, but with much faster computation times. The idea behind deep CNN-based dose estimation can be safely extended to other radiation sources and tumor sites by following a similar training process.

Comparison of commercial dosimetric software platforms in patients treated with 177 Lu-DOTATATE for peptide receptor radionuclide therapy.

Abstract: Purpose: The aim of this study was to quantitatively compare five commercial dosimetric software platforms based on the analysis of clinical datasets of patients who benefited from peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE (LUTATHERA® ) Methods: The dosimetric analysis was performed on two patients during two cycles of PRRT with 177 Lu Single photon emission computed tomography/computed tomography images were acquired at 4, 24, 72, and 192 h post injection Reconstructed images were generated using Dosimetry Toolkit® (DTK) from Xeleris™ and HybridRecon-Oncology version_13_Dicom (HROD) from HERMES Reconstructed images using DTK were analyzed using the same software to calculate time-integrated activity coefficients (TIAC), and mean absorbed doses were estimated using OLINDA/EXM V10 with mass correction Reconstructed images from HROD were uploaded into PLANET® OncoDose from DOSIsoft, STRATOS from Phillips, Hybrid Dosimetry Module™ from HERMES, and SurePlan™ MRT from MIM Organ masses, TIACs, and mean absorbed doses were calculated from each application using their recommendations Results: The majority of organ mass estimates varied by <95% between all platforms The highest variability for TIAC results between platforms was seen for the kidneys (282%) for the two patients and the two treatment cycles Relative standard deviations in mean absorbed doses were slightly higher compared with those observed for TIAC, but remained of the same order of magnitude between all platforms Conclusions: When applying a similar processing approach, results obtained were of the same order of magnitude regardless of the platforms used However, the comparison of the performances of currently available platforms is still difficult as they do not all address the same parts of the dosimetric analysis workflow In addition, the way in which data are handled in each part of the chain from data acquisition to absorbed doses may be different, which complicates the comparison exercise Therefore, the dissemination of commercial solutions for absorbed dose calculation calls for the development of tools and standards allowing for the comparison of the performances between dosimetric software platforms

First Evidence for a Dose–Response Relationship in Patients Treated with 166Ho Radioembolization: A Prospective Study

Abstract: 166Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose-response relationship and its association with overall survival for 166Ho radioembolization in patients with liver metastases. Methods: Patients treated in the HEPAR I and II studies who underwent an 18F-FDG PET/CT scan at baseline, a posttreatment 166Ho SPECT/CT scan, and another 18F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment 166Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo-based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose-response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results: Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178-303 Gy; n = 32) and stable disease (147 Gy; 95% CI, 113-191 Gy; n = 28) (P = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87-159 Gy; n = 21) (P = 0.0008). This constitutes a robust absorbed dose-response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161-274 Gy; n = 13) and patients with progressive disease (116 Gy; 95% CI, 81-165 Gy; n = 9) (P = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, P = 0.01). Conclusion: These results confirm a significant absorbed dose-response relationship in 166Ho radioembolization. Treatment response is associated with a higher overall survival.

Technical Note: Comprehensive performance tests of the first clinical real-time motion tracking and compensation system using MLC and jaws

Abstract: PURPOSE To evaluate the performance of the first clinical real-time motion tracking and compensation system using multileaf collimator (MLC) and jaws during helical tomotherapy delivery. METHODS Appropriate mechanical and dosimetry tests were performed on the first clinical real-time motion tracking system (Synchrony on Radixact, Accuray Inc) recently installed in our institution. kV radiography dose was measured by CTDIw using a pencil chamber. Changes of beam characteristics with jaw offset and MLC leaf shift were evaluated. Various dosimeters and phantoms including A1SL ion chamber (Standard Imaging), Gafchromic EBT3 films (Ashland), TomoPhantom (Med Cal), ArcCheck (Sun Nuclear), Delta4 (ScandiDos), with fiducial or high contrast inserts, placed on two dynamical motion platforms (CIRS dynamic motion-CIRS, Hexamotion-ScandiDos), were used to assess the dosimetric accuracy of the available Synchrony modalities: fiducial tracking with nonrespiratory motion (FNR), fiducial tracking with respiratory modeling (FR), and fiducial free (e.g., lung tumor tracking) with respiratory modeling (FFR). Motion detection accuracy of a tracking target, defined as the difference between the predicted and instructed target positions, was evaluated with the root mean square (RMS). The dose accuracy of motion compensation was evaluated by verifying the dose output constancy and by comparing measured and planned (predicted) three-dimensional (3D) dose distributions based on gamma analysis. RESULTS The measured CTDIw for a single radiograph with a 120 kVp and 1.6 mAs protocol was 0.084 mGy, implying a low imaging dose of 8.4 mGy for a typical Synchrony motion tracking fraction with 100 radiographs. The dosimetric effect of the jaw swing or MLC leaf shift was minimal on depth dose (<0.5%) and was <2% on both beam profile width and output for typical motions. The motion detection accuracies, that is, RMS, were 0.84, 1.13, and 0.48 mm for FNR, FR, and FFR, respectively, well within the 1.5 mm recommended tolerance. Dose constancy with Synchrony was found to be within 2%. The gamma passing rates of 3D dose measurements for a variety of Synchrony plans were well within the acceptable level. CONCLUSIONS The motion tracking and compensation using kV radiography, MLC shifting, and jaw swing during helical tomotherapy delivery was tested to be mechanically and dosimetrically accurate for clinical use.

PET-Based Human Dosimetry of 68Ga-NODAGA-Exendin-4, a Tracer for β-Cell Imaging

Abstract: 68Ga-NODAGA-exendin-4 is a promising tracer for β-cell imaging using PET/CT. Possible applications include preoperative visualization of insulinomas and discrimination between focal and diffuse forms of congenital hyperinsulinism. There is also a significant role for this tracer in extending our knowledge on the role of β-cell mass in the pathophysiology of type 1 and type 2 diabetes by enabling noninvasive quantification of tracer uptake as a measure for β-cell mass. Calculating radiation doses from this tracer is important to assess its safety for use in patients (including young children) with benign diseases and healthy individuals. Methods: Six patients with hyperinsulinemic hypoglycemia were included. After intravenous injection of 100 MBq of the tracer, 4 successive PET/CT scans were obtained at 30, 60, 120, and 240 min after injection. Tracer activity in the pancreas, kidneys, duodenum, and remainder of the body were determined, and time-integrated activity coefficients for the measured organs were calculated. OLINDA/EXM software, version 1.1, was applied to calculate radiation doses using the reference adult male and female models and to estimate radiation doses to children. Results: The mean total effective dose for adults was very low (0.71 ± 0.07 mSv for a standard injected dose of 100 MBq). The organ with the highest absorbed dose was the kidney (47.3 ± 10.2 mGy/100 MBq). The estimated effective dose was 2.32 ± 0.32 mSv for an injected dose of 20 MBq in newborns. This dose decreased to 0.77 ± 0.11 mSv/20 MBq for 1-y-old children and 0.59 ± 0.05 mSv for an injected dose of 30 MBq in 5-y-old children. Conclusion: Our human PET/CT-based dosimetric calculations show that the effective radiation doses from the novel tracer 68Ga-NODAGA-exendin-4 are very low for adults and children. The doses are lower than reported for other polypeptide tracers such as somatostatin analogs (2.1-2.6 mSv/100 MBq) and are beneficial for application as a research tool, especially when repeated examinations are needed.

Determination of consensus k Q values for megavoltage photon beams for the update of IAEA TRS-398.

Abstract: The IAEA is currently coordinating a multi-year project to update the TRS-398 Code of Practice for the dosimetry of external beam radiotherapy based on standards of absorbed dose to water. One major aspect of the project is the determination of new beam quality correction factors, k Q , for megavoltage photon beams consistent with developments in radiotherapy dosimetry and technology since the publication of TRS-398 in 2000. Specifically, all values must be based on, or consistent with, the key data of ICRU Report 90. Data sets obtained from Monte Carlo (MC) calculations by advanced users and measurements at primary standards laboratories have been compiled for 23 cylindrical ionization chamber types, consisting of 725 MC-calculated and 179 experimental data points. These have been used to derive consensus k Q values as a function of the beam quality index TPR20,10 with a combined standard uncertainty of 0.6%. Mean values of MC-derived chamber-specific [Formula: see text] factors for cylindrical and plane-parallel chamber types in 60Co beams have also been obtained with an estimated uncertainty of 0.4%.

177Lu-DOTATATE peptide receptor radionuclide therapy : dose response in small intestinal neuroendocrine tumors

Abstract: Introduction Peptide receptor radionuclide therapy (PRRT) has during the last few years been frequently used in patients with progressive, disseminating, well-differentiated neuroendocrine tumors (NETs). Objective To study whether the absorbed dose in small intestinal NET (SI-NET) metastases from PRRT with 177Lu-DOTATATE is related to tumor shrinkage. Materials and methods Dosimetry for 1 tumor was performed in each of 25 SI-NET patients based on sequential SPECT/CT 1, 4, and 7 days after 177Lu-DOTATATE infusion. The SPECT data were corrected for the partial volume effect based on previous phantom measurements, and the unit density sphere model from OLINDA was used for absorbed dose calculations. Morphological therapy response was assessed by CT/MRI regarding tumor diameter, tumor volume, total liver tumor volume, liver volume, and overall tumor response according to RECIST 1.1. Plasma chromogranin A and urinary 5-hydroxy-indole-acetic-acid were measured during PRRT and follow-up to assess biochemical response. Results At the time of best response with respect to tumor diameter and volume shrinkage, the median absorbed dose was 128.6 Gy (range 28.4-326.9) and 140 Gy (range 50.9-487.4), respectively. All metrics regarding tumor shrinkage and biochemical response were unrelated to the absorbed dose. A correlation was, however, found between the administered radioactivity and the tumor volume shrinkage (p = 0.01) and between the administered radioactivity and RECIST 1.1 response (p = 0.01). Conclusions It was not possible to demonstrate a tumor dose-response relationship in SI-NET metastases with the applied dosimetry method, contrary to what was previously shown for pancreatic NETs.