Behaviour and fluxes of natural radionuclides in the production process of a phosphoric acid plant

In recent years there has been an increasing awareness of the occupational and public hazards of the radiological impact of non-nuclear industries which process materials containing naturally occurring radionuclides. These include the industries devoted to the production of phosphoric acid by treating sedimentary phosphate rocks enriched in radionuclides from the uranium series.With the aim of evaluating the radiological impact of a phosphoric acid factory located in the south-western Spain, the distribution and levels of radionuclides in the materials involved in its production process have been analysed. In this way, it is possible to asses the flows of radionuclides at each step and to locate those points where a possible radionuclide accumulation could be produced. A set of samples collected along the whole production process were analysed to determine their radionuclide content by both alpha-particle and gamma spectrometry techniques. The radionuclide fractionation steps and enrichment sources have been located, allowing the establishment of their mass (activity) balances per year.     

Co-registration of cone beam CT and planning CT in head and neck IMRT dose estimation: a feasible adaptive radiotherapy strategy

Objective:

To investigate if cone beam CT (CBCT) can be used to estimate the delivered dose in head and neck intensity-modulated radiotherapy (IMRT).

Methods:

15 patients (10 without replan and 5 with replan) were identified retrospectively. Weekly CBCT was co-registered with original planning CT. Original high-dose clinical target volume (CTV1), low-dose CTV (CTV2), brainstem, spinal cord, parotids and external body contours were copied to each CBCT and modified to account for anatomical changes. Corresponding planning target volumes (PTVs) and planning organ-at-risk volumes were created. The original plan was applied and calculated using modified per-treatment volumes on the original CT. Percentage volumetric, cumulative (planned dose delivered prior to CBCT + adaptive dose delivered after CBCT) and actual delivered (summation of weekly adaptive doses) dosimetric differences between each per-treatment and original plan were calculated.

Results:

There was greater volumetric change in the parotids with an average weekly difference of between −4.1% and −27.0% compared with the CTVs/PTVs (−1.8% to −5.0%). The average weekly cumulative dosimetric differences were as follows: CTV/PTV (range, −3.0% to 2.2%), ipsilateral parotid volume receiving ≥26 Gy (V26) (range, 0.5–3.2%) and contralateral V26 (range, 1.9–6.3%). In patients who required replan, the average volumetric reductions were greater: CTV1 (−2.5%), CTV2 (−6.9%), PTV1 (−4.7%), PTV2 (−11.5%), ipsilateral (−10.4%) and contralateral parotids (−12.1%), but did not result in significant dosimetric changes.

Conclusion:

The dosimetric changes during head and neck simultaneous integrated boost IMRT do not necessitate adaptive radiotherapy in most patients.

Advances in knowledge:

Our study shows that CBCT could be used for dose estimation during head and neck IMRT.Radiotherapy alone or chemoradiation is used in the primary treatment of head and neck squamous cell carcinomas (HNSCCs). Intensity-modulated radiotherapy (IMRT) allows dose conformality and organ-at-risk (OAR) avoidance in the complex head and neck anatomical region and is therefore the standard of care.¹ IMRT has been proven to reduce the risk of late xerostomia with no detrimental effect on local control or survival.² Changes in gross target volume (GTV) due to treatment response or patient contour secondary to weight loss can lead to dosimetric inaccuracies.^3,4 Because of the greater conformality of IMRT, these changes can have more severe dosimetric impact.¹ This is pertinent to patients receiving curative radiotherapy for HNSCC as delivery is protracted over 6–7 weeks but is based on a single anatomical snapshot acquired during the planning CT scan. Studies have shown that GTVs shrink by 1.8–3.9% per day and parotids shrink by 0.6–1.1% per day.^3,5,6 This coupled with weight loss during treatment could result in a loose immobilization device, thus increasing the set-up uncertainty.^1,3 These progressive anatomical and volumetric changes may have dosimetric consequences and subsequent clinical impact despite the theoretical advantages of IMRT. Clinical significance is determined not only by the level of dosimetric difference, typically defined as ±5%, but also the impact that these may have on the respective target volumes and OARs.Adaptive radiotherapy (ART) has been advocated to overcome some of the problems associated with IMRT in head and neck cancers by modifying treatment plans in response to patient-specific changes during radiotherapy.⁷ This strategy involves modification of the original radiotherapy treatment volumes and plans in response to progressive tumour or normal tissue changes.^7,8 Although ART can be performed online or offline, the latter strategy is probably more applicable in the busy clinical setting. ART requires the availability of image-guided radiotherapy using on-board imaging such as kilovoltage (kV) or megavoltage (MV) cone beam CT (CBCT), or in-room kV CT to detect tumour or normal tissue changes. However, not all patients derive a clinically significant benefit from ART.^9,10 In addition, this strategy is labour and resource intensive, which could affect its widespread clinical implementation. As such, attempts should be made to identify the subset of patients who will benefit from ART as this could potentially improve disease control and reduce toxicities, without imposing a great stress on current radiotherapy resources.¹¹Image-guided IMRT using kV CBCT is routinely used in our centre for HNSCC patients receiving curative radiotherapy. We hypothesize that the co-registration of regular CBCT and planning CT scans could be used to estimate delivered doses in these patients. This may allow identification of a cohort of patients with significant volumetric and, more importantly, dosimetric changes who may benefit from ART.     

Comparison of high-dose rate prostate brachytherapy dose distributions with iridium-192, ytterbium-169, and thulium-170 sources

Purpose

Recent studies have identified that among different available radionuclides, the dose characteristics and shielding properties of ytterbium-169 (¹⁶⁹Yb) and thulium-170 (¹⁷⁰Tm) may suit high-dose rate (HDR) brachytherapy needs. The purpose of this work was to compare clinically optimized dose distributions using proposed ¹⁶⁹Yb and ¹⁷⁰Tm HDR sources with the clinical dose distribution from a standard microSelectron V2 HDR iridium-192 (¹⁹²Ir) brachytherapy source (Nucletron B.V., Veenendaal, The Netherlands).

Methods and materials

CT-based treatment plans of 10 patients having prostate volumes ranging from 17 to 92 cm³ were studied retrospectively. Clinical treatment of these patients involved 16 catheters and a microSelectron V2 HDR ¹⁹²Ir source. All dose plans were generated with inverse planning simulated annealing optimization algorithm. Dose objectives used for the ¹⁹²Ir radionuclide source were used for the other two radionuclides. The dose objective parameters were adjusted to obtain the same clinical target (prostate) volume coverage as the original ¹⁹²Ir radionuclide plan. A complete set of dosimetric indices was used to compare the plans from different radionuclides. A pairwise statistical analysis was also performed.

Results and conclusions

All the dose distributions optimized with specific ¹⁹²Ir, ¹⁶⁹Yb, and ¹⁷⁰Tm sources satisfied the standard clinical criteria for HDR prostate implants, such as those for the Radiation Therapy Oncology Group clinical trial 0321, for combined HDR and external beam treatment for prostate adenocarcinoma. For equivalent clinical target volume dose coverage, the specific ¹⁶⁹Yb and ¹⁷⁰Tm sources resulted in a statistically significant dose reduction to organs at risk compared with microSelectron V2 HDR ¹⁹²Ir source. This study indicates that a ¹⁷⁰Tm or ¹⁶⁹Yb radionuclide source may be an alternative to the ¹⁹²Ir radionuclide sources in HDR brachytherapy.     

Influence of Pro-Qura–generated Plans on Postimplant Dosimetric Quality: A Review of a Multi-Institutional Database

The influence of Pro-Qura–generated plans vs. community-generated plans on postprostate brachytherapy dosimetric quality was compared. In the Pro-Qura database, 2933 postplans were evaluated from 57 institutions. A total of 1803 plans were generated by Pro-Qura and 1130 by community institutions. Iodine-125 (¹²⁵I) plans outnumbered Palladium 103 (¹⁰³Pd) plans by a ratio of 3:1. Postimplant dosimetry was performed in a standardized fashion by overlapping the preimplant ultrasound and the postimplant computed tomography (CT). In this analysis, adequacy was defined as a V₁₀₀ > 80% and a D₉₀ of 90% to 140% for both isotopes along with a V₁₅₀ < 60% for ¹²⁵I and < 75% for ¹⁰³Pd. The mean postimplant V₁₀₀ and D₉₀ were 88.6% and 101.6% vs. 89.3% and 102.3% for Pro-Qura and community plans, respectively. When analyzed in terms of the first 8 sequence groups (10 patients/sequence group) for each institution, Pro-Qura planning resulted in less postimplant variability for V₁₀₀ (86.2–89.5%) and for D₉₀ (97.4–103.2%) while community-generated plans had greater V₁₀₀ (85.3–91.2%) and D₉₀ (95.9–105.2%) ranges. In terms of sequence groups, postimplant dosimetry was deemed “too cool” in 11% to 30% of cases and “too hot” in 12% to 27%. On average, no clinically significant postimplant dosimetric differences were discerned between Pro-Qura and community-based planning. However, substantially greater variability was identified in the community-based plan cohort. It is possible that the Pro-Qura plan and/or the routine postimplant dosimetric evaluation may have influenced dosimetric outcomes at community-based centers.     

Evaluation of Dosimetric Parameters for Various Ir Brachytherapy Sources Under Unbounded Phantom Geometry by Monte Carlo Simulation

As per TG-43 dose calculation formalism, it is essential to obtain various dosimetric parameters such as the air-kerma strength, dose rate constant, radial dose function, and anisotropy function, as they account for accurate determination of dose rate distribution around brachytherapy sources. Most of the available reported Monte Carlo simulations were performed in liquid water phantoms with a bounded region of 30-cm diameter. In this context, an attempt was made to report the dosimetric parameters for various commercially available pulsed-dose rate (PDR) and high-dose rate (HDR) sources under unbounded phantom conditions, as the data may be used as input to treatment planning systems (TPSs) for quality control assistance. The air-kerma strength per unit activity, S_k/A, was computed for various Iridium-192 (¹⁹²Ir) sources in dry air medium. The air-kerma strength and dose rate constant for old PDR is (9.77 ± 0.03) 10⁻⁸ U/Bq and 1.124 ± 0.001 cGyh⁻¹U⁻¹; for new PDR, the values are (9.96 ± 0.03) 10⁻⁸ U/Bq and 1.124 ± 0.001 cGyh⁻¹U⁻¹; for old MHDR, the values are (9.80 ± 0.01) 10⁻⁸ U/Bq and 1.115 ± 0.001 cGyh⁻¹U⁻¹; for new MHDR, (9.80 ± 0.01) 10⁻⁸ U/Bq and 1.112 ± 0.001cGyh⁻¹U⁻¹; for old VHDR, the values are (10.32 ± 0.01) 10⁻⁸ U/Bq and 1.035 ± 0.002 cGyh⁻¹U⁻¹; for new VHDR, the values are (10.34 ± 0.02) 10⁻⁸ U/Bq and 1.096 ± 0.001 cGyh⁻¹U⁻¹. The computed radial dose function values and anisotropy function values are also in good agreement with available data.     

Optimisation study of α-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes

The production of no-carrier-added (NCA) α-emitter ²¹¹At/^211gPo radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the ²⁰⁹Bi(α,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the γ-emitter ²¹⁰At and its long half-lived α-emitting daughter ²¹⁰Po is optimised and minimised by appropriate choice of energy and energy loss of α particle beam. The measured excitation functions for production of the main radioisotopic impurity ²¹⁰At→²¹⁰Po are compared with theoretical predictions from model calculations performed at ENEA.     

Cell Irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences

Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings.Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.     

Correlation between gamma index passing rate and clinical dosimetric difference for pre-treatment 2D and 3D volumetric modulated arc therapy dosimetric verification

Objective:

To investigate comparatively the percentage gamma passing rate (%GP) of two-dimensional (2D) and three-dimensional (3D) pre-treatment volumetric modulated arc therapy (VMAT) dosimetric verification and their correlation and sensitivity with percentage dosimetric errors (%DE).

Methods:

%GP of 2D and 3D pre-treatment VMAT quality assurance (QA) with different acceptance criteria was obtained by ArcCHECK® (Sun Nuclear Corporation, Melbourne, FL) for 20 patients with nasopharyngeal cancer (NPC) and 20 patients with oesophageal cancer. %DE were calculated from planned dose–volume histogram (DVH) and patients'' predicted DVH calculated by 3DVH® software (Sun Nuclear Corporation). Correlation and sensitivity between %GP and %DE were investigated using Pearson''s correlation coefficient (r) and receiver operating characteristics (ROCs).

Results:

Relatively higher %DE on some DVH-based metrics were observed for both patients with NPC and oesophageal cancer. Except for 2%/2 mm criterion, the average %GPs for all patients undergoing VMAT were acceptable with average rates of 97.11% ± 1.54% and 97.39% ± 1.37% for 2D and 3D 3%/3 mm criteria, respectively. The number of correlations for 3D was higher than that for 2D (21 vs 8). However, the general correlation was still poor for all the analysed metrics (9 out of 26 for 3D 3%/3 mm criterion). The average area under the curve (AUC) of ROCs was 0.66 ± 0.12 and 0.71 ± 0.21 for 2D and 3D evaluations, respectively.

Conclusions:

There is a lack of correlation between %GP and %DE for both 2D and 3D pre-treatment VMAT dosimetric evaluation. DVH-based dose metrics evaluation obtained from 3DVH will provide more useful analysis.

Advances in knowledge:

Correlation and sensitivity of %GP with %DE for VMAT QA were studied for the first time.Volumetric modulated arc therapy (VMAT) is a novel delivery method of intensity-modulated radiotherapy (IMRT). It is capable of delivering highly conformal dose distributions through concomitant continuous gantry rotation, dynamic beam modulation and variable dose rate.^1,2 Owing to its rotational delivery features, VMAT is more complex than conventional IMRT in both planning and dosimetric evaluations.^3,4Quality assurance (QA) for VMAT is relatively new with respect to the established dosimetric verification of fixed-beam IMRT with two-dimensional (2D) arrays. Verifying the whole plan while the gantry is rotating is rather challenging.^5,6 Numerous approaches and phantoms have been investigated for the QA of VMAT, including Monte Carlo simulation,⁷ ScandiDos Delta⁴® (ScandiDos, Uppsala, Sweden),⁸ GAFCHROMIC® EBT (International Specialty Products, Wayne, NJ) films,⁹ MatriXX™ 2D ionization chamber array with a MultiCube™ phantom (IBA Dosimetry Inc., Memphis, TN),¹⁰ 2D-ARRAT seven29 and Octavius phantom (PTW, Freiburg, Germany), electronic portal imaging device and three-dimensional (3D) diode array ArcCHECK® (Sun Nuclear Corporation, Melbourne, FL).⁶Until now, no standardized QA procedure and acceptance criteria specific for VMAT have been established. Those performing VMAT QA are typically using QA methods and action levels taken from fixed-beam IMRT QA methods. Phantom dose verification, gamma index with 3% dose difference and 3-mm dose-to-distance criteria are most commonly used by physicists in pre-treatment IMRT and VMAT QA as reported in the AAPM Task Group 119 and some other articles.^11–13 However, recent studies demonstrated that there is no correlation between the percentage gamma passing rate (%GP) and the magnitude of dose discrepancy between the planned dose and the actual delivered dose for IMRT.^14,15 This also raises concern about whether the %GP is correlated with clinical dosimetric difference for VMAT.The main purpose of this study is to investigate comparatively the %GP of 2D and 3D VMAT dosimetric verification with different acceptance criteria, and their correlation and sensitivity with percentage dosimetric errors (%DE) between planned dose–volume histogram (DVH) and patients'' predicted DVH calculated by 3DVH® software (Sun Nuclear Corporation).     

Cell irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences

Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings. Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.     

Assessment and quantification of patient set-up errors in nasopharyngeal cancer patients and their biological and dosimetric impact in terms of generalized equivalent uniform dose (gEUD), tumour control probability (TCP) and normal tissue complication probability (NTCP)

Objective:

The aim of this study is to assess and quantify patients'' set-up errors using an electronic portal imaging device and to evaluate their dosimetric and biological impact in terms of generalized equivalent uniform dose (gEUD) on predictive models, such as the tumour control probability (TCP) and the normal tissue complication probability (NTCP).

Methods:

20 patients treated for nasopharyngeal cancer were enrolled in the radiotherapy–oncology department of HCA. Systematic and random errors were quantified. The dosimetric and biological impact of these set-up errors on the target volume and the organ at risk (OARs) coverage were assessed using calculation of dose–volume histogram, gEUD, TCP and NTCP. For this purpose, an in-house software was developed and used.

Results:

The standard deviations (1SDs) of the systematic set-up and random set-up errors were calculated for the lateral and subclavicular fields and gave the following results: ∑ = 0.63 ± (0.42) mm and σ = 3.75 ± (0.79) mm, respectively. Thus a planning organ at risk volume (PRV) margin of 3 mm was defined around the OARs, and a 5-mm margin used around the clinical target volume. The gEUD, TCP and NTCP calculations obtained with and without set-up errors have shown increased values for tumour, where ΔgEUD (tumour) = 1.94% Gy (p = 0.00721) and ΔTCP = 2.03%. The toxicity of OARs was quantified using gEUD and NTCP. The values of ΔgEUD (OARs) vary from 0.78% to 5.95% in the case of the brainstem and the optic chiasm, respectively. The corresponding ΔNTCP varies from 0.15% to 0.53%, respectively.

Conclusion:

The quantification of set-up errors has a dosimetric and biological impact on the tumour and on the OARs. The developed in-house software using the concept of gEUD, TCP and NTCP biological models has been successfully used in this study. It can be used also to optimize the treatment plan established for our patients.

Advances in knowledge:

The gEUD, TCP and NTCP may be more suitable tools to assess the treatment plans before treating the patients.The main goal of radiation therapy planning is to maximize dose to the target while minimizing dose to the nearby healthy organs, in order to improve the control of tumour growth and to reduce side effects. Nasopharyngeal cancer is common in North Africa, especially in Algeria. It is the highest cause of death among head and neck cancer patients according to “Registre du cancer”.¹ Recently, a three-dimensional conformal radiotherapy (3D-CRT) technique has been implemented in the radiotherapy–oncology department of the Mohamed Seghir Nekkache hospital (HCA) in Algiers.In order to evaluate and to achieve the most optimized treatment plans, predictive models that describe the relationship between dose distributions in organs at risk (OARs) and the probability of radiation-induced complications are needed,² especially those resulting from patient set-up errors. Of course, it is an increasingly important part of the clinical radiotherapy process, for which set-up errors consist of both a systematic component and a random component. The former happens when we have the same deviation in the same direction for each fraction throughout the whole course of treatment, while random errors vary from day-to-day.³ One way to diminish systematic as well as random set-up deviations is to use electronic portal imaging devices (EPIDs). Effectively, the EPIDs have become available in a large number of institutions for the sake of determining the set-up errors over previous years.^4–6In our study, both types of systematic and random errors were investigated for 20 nasopharynx radiotherapy patients by applying EPIDs. Patient set-up error evaluation in head and neck cancers constitute a challenge partly because the planning target volume (PTV) and the planning organ-at-risk volume (PRV) margins must be specified.⁷Unfortunately, when set-up errors occur and a PTV is surrounding the OARs, the dose distributions are not always uniform. In this case, tools are needed to evaluate treatment plans in 3D-CRT.⁸ One way this can be used consists of converting dose–volume histograms (DVHs) to an equivalent uniform dose (EUD),⁹ and then estimating the tumour control probability (TCP) and the normal tissue complication probability (NTCP).^10,11The concept of EUD, introduced by Niemierko,¹² was originally defined as the absorbed dose, that is, if given uniformly, would lead to the same cell death as the actual non-uniform absorbed-dose distribution. The current definition of EUD is the generalized mean absorbed dose. According to Niemierko who generalized its application to normal structures and tumours, the concept of EUD has been used as one of the several metrics to determine the impact of absorbed-dose heterogeneity on normal tissues and tumours. EUD is also well suited for obtaining the biological effect for the heterogeneous irradiation of a volume of interest,¹³ whereas TCP and NTCP are predictive models that will be affected by set-up errors and organ motion.¹⁴     

Sexual organ-sparing with hydrogel spacer injections for rectal cancer radiotherapy: a feasibility pilot study

Objectives:The aim of this pilot study was to investigate in two rectal cancer patients undergoing neoadjuvant chemo-radiotherapy (nCRT) the implant feasibility and dosimetric benefit in sexual organ-sparing of an injectable, absorbable, radiopaque hydrogel spacer.Methods:Two rectal cancer patients (one male and one female) underwent hydrogel implant between rectum and vagina/prostate before nCRT and curative surgery. A CT scan was performed before and after injection and a comparative dosimetric study was performed testing a standard (45/50 Gy) and a dose escalated (46/55.2 Gy) schedule.Results:In both patients, the spacer implant in the recto-prostatic or recto-vaginal space was feasible and well tolerated. For the male, the dosimetric benefit with spacer was minimal for sexual organs. For the female however, doses delivered to the vagina were significantly reduced with spacer with a mean reduction of more than 5 Gy for both regimens.Conclusions:For organ preservation protocols and selected sexually active female patients, use of hydrogel spacers can be considered to spare sexual organs from the high radiotherapy dose levels.Advances in knowledge:For females with advanced rectal tumor, a spacer implant between the rectum and the vagina before nCRT is feasible and reduces doses delivered to the vagina.     

Validation of a dose warping algorithm using clinically realistic scenarios

Objective:

Dose warping following deformable image registration (DIR) has been proposed for interfractional dose accumulation. Robust evaluation workflows are vital to clinically implement such procedures. This study demonstrates such a workflow and quantifies the accuracy of a commercial DIR algorithm for this purpose under clinically realistic scenarios.

Methods:

12 head and neck (H&N) patient data sets were used for this retrospective study. For each case, four clinically relevant anatomical changes have been manually generated. Dose distributions were then calculated on each artificially deformed image and warped back to the original anatomy following DIR by a commercial algorithm. Spatial registration was evaluated by quantitative comparison of the original and warped structure sets, using conformity index and mean distance to conformity (MDC) metrics. Dosimetric evaluation was performed by quantitative comparison of the dose–volume histograms generated for the calculated and warped dose distributions, which should be identical for the ideal “perfect” registration of mass-conserving deformations.

Results:

Spatial registration of the artificially deformed image back to the planning CT was accurate (MDC range of 1–2 voxels or 1.2–2.4 mm). Dosimetric discrepancies introduced by the DIR were low (0.02 ± 0.03 Gy per fraction in clinically relevant dose metrics) with no statistically significant difference found (Wilcoxon test, 0.6 ≥ p ≥ 0.2).

Conclusion:

The reliability of CT-to-CT DIR-based dose warping and image registration was demonstrated for a commercial algorithm with H&N patient data.

Advances in knowledge:

This study demonstrates a workflow for validation of dose warping following DIR that could assist physicists and physicians in quantifying the uncertainties associated with dose accumulation in clinical scenarios.Modern radiotherapy aims to move towards a personalized treatment for each patient with cancer, requiring reliable predictions of an individual''s response to a particular therapy and accurate monitoring of treatment delivery, enabling adaptations to the treatment plan as required. To date, typical radiotherapy practice involves the preparation of a treatment plan based on an initial high resolution CT scan of the anatomy to be treated. However, since the treatment is optimized for the anatomy on planning CT (pCT), any changes in a patient''s anatomy during the treatment course itself (which may last for up to 8 weeks) could result in a suboptimal treatment. Currently, to account for interfraction movements, a low-resolution, low-dose CT image [typically cone beam CT (CBCT) or mega-voltage CT (MVCT), although other options exist] of the patient is often acquired prior to each treatment (daily images). This is termed image-guided radiotherapy (IGRT).¹In 1997, Yan et al² proposed the concept of adaptive radiotherapy (ART), suggesting the adaptation of the treatment plan to account for interfraction anatomical variations, based on these daily images. Such treatment adaptations are sometimes currently employed in routine clinical practice when significant anatomical changes are observed, such as substantial weight loss.³ State-of-the-art ART, on the other hand, aims to regularly monitor the treatment delivery and adapt when necessary (offline ART)² or even predict the result and alter it before the treatment of that day (online ART).⁴ The ability to determine the accumulated delivered dose to deforming anatomy is of vital importance not only for ART but also for the assessment and optimization of radiobiological models,⁵ since without it, these models are informed by less accurate estimates of delivered dose to each tissue or partial tissue volume. However, certain limitations such as inaccuracies in contour propagation and in reliable dose accumulation currently prevent efficient routine monitoring of delivered dose throughout the treatment.Deformable image registration (DIR) algorithms have been proposed as a method for facilitating these processes. The accuracy of DIR algorithms is therefore of critical importance and has been the subject of investigation by several researchers, with mechanical phantoms,^6–13 patient images^14–22 and digital phantoms (i.e. patient images artificially deformed with known deformations)^10,11,23 being extensively used for DIR assessment.An extension to these issues is the application of the underlying anatomical deformations to a calculated dose distribution, which is a necessary step in interfractional dose accumulation. Such dose warping process involves the direct deformation of a calculated dose distribution by applying the deformation matrix estimated during DIR between two anatomical scans, essentially warping the dose according to the reference anatomy. Dose warping and deformable dose accumulation have been employed in a number of clinical investigations, including a dose feedback technique in ART frameworks,²⁴ the assessment of planning target volume (PTV) margins²⁵ and the examination of parotid gland dose–effect relationships,²⁶ based on dose distributions recalculated on daily or weekly scans and the accumulation on a single frame of reference. Consequently, quality assurance and evaluation techniques have been investigated in order to validate the applicability of this dose warping concept. Previous work has investigated mathematical models to directly convert DIR errors into dose-warping uncertainties, through the use of patient images and mechanical or digital phantoms,^15,27–30 while a number of deformable dosimetric and non-dosimetric gel phantoms have been produced enabling the experimental evaluation of both DIR and dose warping.^31–35 Even though some of these studies revealed promising results, they have not convinced the radiotherapy community that these uncertainties are adequately understood.³⁶In one such study, Yeo et al³⁴ used a cylindrical deformable dosimetric gel phantom for the experimental validation of dose warping against actual three-dimensional (3D) measurements. The warped and measured dose distributions revealed an agreement of 3D γ_3%/3mm = 99.9%, after small deformations (approximately 9 mm), and γ_3%/3 mm = 96.7% after larger deformations (approximately 20 mm). The authors therefore concluded that “dose-warping may be justified for small deformations in particular and those that do not involve significant density changes”. On the other hand, Juang et al³⁵ exposed “substantial errors in a commercial DIR” used for dose-warping evaluation, utilizing another 3D deformable dosimetric gel, revealing a 3D γ_3%/3mm passing rate of 60%.Such studies, and especially the use of deformable dosemeters for the evaluation of dose warping, are very important as they can reveal the 3D dosimetric impact owing to the uncertainties of a given DIR algorithm. However, they possess three important limitations: first, typical physical dosimetric phantoms present limited image complexity and would not assess the performance limits of the DIR algorithm under evaluation in clinical scenarios. Second, plan delivery, intrinsic dosimetric and dose reading uncertainties are present when using any type of dosemeter in physical phantom measurements. The third limitation is the fact that even where such approaches can offer high precision dosimetric uncertainty evaluation, they cannot directly inform users about the potential extent of those uncertainties in practical clinical cases. All these issues will be addressed in this work.In the present study, a workflow for the robust validation of DIR and dose warping is presented, using patient images artificially deformed with clinically realistic deformations and clinically optimized Monte Carlo dose calculations of intensity-modulated radiotherapy (IMRT) plans, quantifying both the spatial errors in the deformable registration and their dosimetric impact when applied to dose accumulation. In contrast to previously proposed evaluation procedures, this method examines and reports dose-warping uncertainties under clinically relevant scenarios. Although the validation workflow is applicable for different DIRs and clinical indications, it is here employed specifically for the evaluation of a commercial software (OnQ rts^®; Oncology Systems Limited, Shropshire, UK) in head and neck (H&N) cancer patient cases.     

Biokinetic and dosimetric studies of Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical.

Methods

¹⁸⁸Re-HA was prepared by a direct labelling method to produce a ReO(O-COO)₂-type coordination complex. ¹⁸⁸Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of ¹⁸⁸Re-HA was determined.

Results

A stable complex of ¹⁸⁸Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T_1/2α=21 min). Four hours after administration, ¹⁸⁸Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47±5.11% of the injected dose). The liver MTD in mice was 40 Gy after 7.4 MBq of ¹⁸⁸Re-HA injection.

Conclusions

¹⁸⁸Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.     

共面模板辅助125I粒子植入治疗肺癌术后局部复发的剂量学研究

目的评价通用共面模板(以下简称通用模板)辅助CT引导下对肺癌术后局部复发进行¹²⁵I放射性粒子治疗的植入前、植入后剂量学符合程度及对疗效的影响。方法收集自2009年1月至2015年12月在天津医科大学第二医院接受通用模板辅助¹²⁵I放射性粒子植入治疗的非小细胞肺癌术后局部复发患者38例。术前进行预计划,处方剂量110 Gy。术中验证结果与术前计划的剂量参数匹配周边剂量(MPD)、90%靶体积的最小吸收剂量(D90)、100%靶体积的最小吸收剂量(D100)、适形指数(CI)、靶区外体积指数(EI)和均匀性指数(HI)进行配对t检验。术后第6个月按照实体肿瘤疗效评价标准(1.1版)判定疗效。结果全部患者完成粒子植入治疗,术前计划、术后质量验证剂量:MPD为(222.7±26.2)、(227.7±29.8)Gy,D90(130.8±13.6)、(134.8±12.8)Gy,D100(106.4±10.6)、(110.7±11.8)Gy,CI(0.75±0.06)、(0.74±0.04),EI(22.7±5.8)%、(24.3±4.8)%,HI(36.8±4.7)%、(37.2±5.3)%,心脏平均照射剂量为(19.3±7.2)、(21.3±6.8)Gy(P>0.05),中位随访时间为22.5个月(8~98个月)。中位生存期21个月(95%CI 7.4~34.6),2年总生存(OS),无进展生存(PFS)和局部控制(LC)的发生率分别为47.4%、39.5%和83.5%。结论通用模板辅助CT引导下¹²⁵I放射性粒子植入治疗非小细胞肺癌术后局部复发可以较好地在术中实现术前TPS计划目标,取得良好疗效,是一种微创、精准、安全、有效的治疗方法。     

Dose attenuation effect of hip prostheses in a 9-MV photon beam: commercial treatment planning system versus Monte Carlo calculations

Purpose The purpose of this study was to investigate the dosimetric effect of various hip prostheses on pelvis lateral fields treated by a 9-MV photon beam using Monte Carlo (MC) and effective path-length (EPL) methods. Material and methods The head of the Neptun 10 pc linac was simulated using the MCNP4C MC code. The accuracy of the MC model was evaluated using measured dosimetric features including depth dose values and dose profiles in a water phantom. The Alfard treatment planning system (TPS) was used for EPL calculations. A virtual water phantom with dimensions of 30 × 30 × 30 cm³ and a cube with dimensions of 4 × 4 × 4 cm³ made of various metals centered in 12 cm depth was used for MC and EPL calculations. Various materials including titanium, Co-Cr-Mo, and steel alloys were used as hip prostheses. Results Our results showed significant attenuation in absorbed dose for points after and inside the prostheses. Attenuations of 32%, 54% and 55% were seen for titanium, Co-Cr-Mo, and steel alloys, respectively, at a distance of 5 cm from the prosthesis. Considerable dose increase (up to 18%) was found at the water–prosthesis interface due to back-scattered electrons using the MC method. The results of EPL calculations for the titanium implant were comparable to the MC calculations. This method, however, was not able to predict the interface effect or calculate accurately the absorbed dose in the presence of the Co-Cr-Mo and steel prostheses. Conclusion The dose perturbation effect of hip prostheses is significant and cannot be predicted accurately by the EPL method for Co-Cr-Mo or steel prostheses. The use of MC-based TPS is recommended for treatments requiring fields passing through hip prostheses.     

RapidPlan hippocampal sparing whole brain model version 2—how far can we reduce the dose?

Whole-brain radiotherapy has been the standard palliative treatment for patients with brain metastases due to its effectiveness, availability, and ease of administration. Recent clinical trials have shown that limiting radiation dose to the hippocampus is associated with decreased cognitive toxicity. In this study, we updated an existing Knowledge Based Planning model to further reduce dose to the hippocampus and improve other dosimetric plan quality characteristics. Forty-two clinical cases were contoured according to guidelines. A new dosimetric scorecard was created as an objective measure for plan quality. The new Hippocampal Sparing Whole Brain Version 2 (HSWBv2) model adopted a complex recursive training process and was validated with five additional cases. HSWBv2 treatment plans were generated on the Varian Halcyon^TM and TrueBeam^TM systems and compared against plans generated from the existing (HSWBv1) model released in 2016. On the Halcyon^TM platform, 42 cases were re-planned. Hippocampal D_100% from HSWBv2 and HSWBv1 models had an average dose of 5.75 Gy and 6.46 Gy, respectively (p < 0.001). HSWBv2 model also achieved a hippocampal D_mean of 7.49 Gy, vs 8.10 Gy in HSWBv1 model (p < 0.001). Hippocampal D_0.03CC from HSWBv2 model was 9.86 Gy, in contrast to 10.57 Gy in HSWBv1 (p < 0.001). For PTV_3000, D_98% and D_2% from HSWBv2 model were 28.27 Gy and 31.81 Gy, respectively, compared to 28.08 Gy (p = 0.020) and 32.66 Gy from HSWBv1 (p < 0.001). Among several other dosimetric quality improvements, there was a significant reduction in PTV_3000 V_105% from 35.35% (HSWBv1) to 6.44% (HSWBv2) (p < 0.001). On 5 additional validation cases, dosimetric improvements were also observed on TrueBeam^TM. In comparison to published data, the HSWBv2 model achieved higher quality hippocampal avoidance whole brain radiation therapy treatment plans through further reductions in hippocampal dose while improving target coverage and dose conformity/homogeneity. HSWBv2 model is shared publicly.     

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

Purpose For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with ⁹⁰Y is frequently used [⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide (considered as the gold standard) and the commercially available ¹¹¹In-pentetreotide.Methods The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide, in accordance with the directives of the German radiation protection authorities.Results The range of doses (mGy/MBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide) for kidneys, spleen, liver and tumour masses was 0.6–2.8, 1.5–4.2, 0.3–1.3 and 2.1–29.5 (⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide), respectively, versus 1.3–3.0, 1.8–4.4, 0.2–0.8 and 1.4–19.7 (¹¹¹In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy.Conclusion Compared with ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide, dosimetry with ¹¹¹In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.     

The impact of air pockets around the vaginal cylinder on vaginal vault brachytherapy

Objective:

To evaluate the incidence, size and predisposing factors for air pockets around the vaginal cylinder and their dosimetric effect on the vaginal mucosa.

Methods:

We investigated 174 patients with endometrial carcinoma treated with external radiotherapy (RT) and brachytherapy (BRT) (101 patients, 58%) or BRT alone (73 patients, 42%). The quantity, volume and dosimetric impact of the air pockets surrounding the vaginal cylinder were quantified. The proportions of patients with or without air pockets during application were stratified according to menopausal status, treatment modality and interval between surgery and RT.

Results:

Air pockets around the vaginal cylinder were seen in 75 patients (43%), while 99 patients (57%) had no air pockets. Only 11 patients (6.3%) received less than the prescribed dose (average 93.9% of prescribed dose; range, 79.0–99.2%). Air pockets were significantly fewer in pre-menopausal patients or in patients treated with the combination of external RT and BRT than in post-menopausal patients or patients treated with BRT alone. A significant correlation existed between the mucosal displacement of the air gap and the ratio of the measured dose at the surface of the air gap and prescribed dose (Pearson r = −0.775; p < 0.001).

Conclusion:

Air pockets were still a frequent problem during vaginal vault BRT, especially in post-menopausal patients or in patients treated with BRT alone, which may potentially cause dose reductions at the vaginal mucosa.

Advances in knowledge:

Air pockets around the vaginal cylinder remain a significant problem, which may potentially cause dose reduction in the target volume.The primary treatment of choice in localized endometrial cancer is surgery. Adjuvant radiotherapy (RT) is recommended in intermediate- and high-risk patients in order to diminish disease recurrence. RT can be in the form of external RT (ERT) with vaginal vault brachytherapy (BRT) or BRT only, depending on the risk factors and stage of disease.The purpose of vaginal vault BRT is to eradicate a microscopic tumour at the lymphatics located in the vaginal vault. It was demonstrated that >90% of lymphatics lie within 2–3 mm from the surface of stretched mucosa.¹ For this reason, in order to deliver adequate doses to the submucosal lymphatics, the vaginal cylinder must be in direct contact with the vaginal surface, as recommended by the American Brachytherapy Society (ABS).² The Group Europeén de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) guidance³ is to prescribe vaginal BRT to 5 mm from the applicator surface with a 2-mm tolerance. The most commonly used applicator for vaginal vault high-dose-rate BRT is a segmented cylinder.⁴ However, during application, air gaps may be observed, which may potentially cause underdosage of the vaginal mucosa.Cameron et al⁵ found that 18 of 25 patients (72%) had air gaps >2 mm in the cranial part of the vagina, with the median number of air pockets per patient being 1 (range, 0–5). Richardson et al⁶ reported that 20 of 25 patients (80%) had at least 1 air pocket in the upper vagina. In another study, Humphrey et al⁷ demonstrated >2 mm air gaps in 11/103 patients, while repositioning or use of a larger cylinder reduced air gaps in 7/103 patients. However, in all of these studies, applicators of different sizes were used with a limited number of patients and conflicting results have been reported.In Baskent University Department of Radiation Oncology, Adana, Turkey, we prefer using cylinders with the largest diameter for reducing air gaps during vaginal vault BRT. The purpose of this study was to evaluate the incidence, size and dosimetric effects of these air pockets. In addition, the predisposing factors for the development of air gaps were analysed.