AAPM Task Group Report 267: A joint AAPM GEC-ESTRO report on biophysical models and tools for the planning and evaluation of brachytherapy.

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments.

Dissipation kinetics, residue modeling and human intake of endosulfan applied to okra (Abelmoschus esculentus).

The non-judicious application of the harmful pesticide endosulfan on okra, one of India's most consumed vegetable crops, has resulted in the frequent detection of residues in food samples. This can lead to resistance and the resurgence of various pests and diseases. In this context, combined dissipation and residue dynamics of different endosulfan components or mixtures (isomers and metabolites) in crop compartments are not yet well understood. To address this research gap, the present study evaluates the dissipation and persistence behavior of different endosulfan isomers (alpha-, beta-isomers) and major metabolite (endosulfan sulfate) on okra during 2017 and 2018. The half-life of endosulfan on okra leaves was found to be between 1.79 and 3.47 days. Half of the endosulfan deposits on okra fruits at the recommended doses were dissipated after 2.39 days compared to 1.99 days at double recommended doses (mean of 2017 and 2018 residue data). Measured endosulfan residues were evaluated against the dynamic plant uptake model dynamiCROP. The better fits were observed between modeled and measured residues for fruits (R2 from 0.84 to 0.96 and residual standard error (ER) between 0.6 and 1.47) as compared to leaves (R2 from 0.57 to 0.88). We also report fractions of endosulfan components ingested by humans after crop harvest. Intake fractions range from 0.0001-7.2 gintake/kg of applied pesticide. Our results can evaluate pesticide residues in different crops grown for human consumption, including their isomers and metabolites. They can be combined with dose-response information to evaluate human exposure and/or health risk assessment.

Recommendations for intraoperative mesh brachytherapy: Report of AAPM Task Group No. 222.

Mesh brachytherapy is a special type of a permanent brachytherapy implant: it uses low-energy radioactive seeds in an absorbable mesh that is sutured onto the tumor bed immediately after a surgical resection. This treatment offers low additional risk to the patient as the implant procedure is carried out as part of the tumor resection surgery. Mesh brachytherapy utilizes identification of the tumor bed through direct visual evaluation during surgery or medical imaging following surgery through radiographic imaging of radio-opaque markers within the sources located on the tumor bed. Thus, mesh brachytherapy is customizable for individual patients. Mesh brachytherapy is an intraoperative procedure involving mesh implantation and potentially real-time treatment planning while the patient is under general anesthesia. The procedure is multidisciplinary and requires the complex coordination of multiple medical specialties. The preimplant dosimetry calculation can be performed days beforehand or expediently in the operating room with the use of lookup tables. In this report, the guidelines of American Association of Physicists in Medicine (AAPM) are presented on the physics aspects of mesh brachytherapy. It describes the selection of radioactive sources, design and preparation of the mesh, preimplant treatment planning using a Task Group (TG) 43-based lookup table, and postimplant dosimetric evaluation using the TG-43 formalism or advanced algorithms. It introduces quality metrics for the mesh implant and presents an example of a risk analysis based on the AAPM TG-100 report. Recommendations include that the preimplant treatment plan be based upon the TG-43 dose calculation formalism with the point source approximation, and the postimplant dosimetric evaluation be performed by using either the TG-43 approach, or preferably the newer model-based algorithms (viz., TG-186 report) if available to account for effects of material heterogeneities. To comply with the written directive and regulations governing the medical use of radionuclides, this report recommends that the prescription and written directive be based upon the implanted source strength, not target-volume dose coverage. The dose delivered by mesh implants can vary and depends upon multiple factors, such as postsurgery recovery and distortions in the implant shape over time. For the sake of consistency necessary for outcome analysis, prescriptions based on the lookup table (with selection of the intended dose, depth, and treatment area) are recommended, but the use of more advanced techniques that can account for real situations, such as material heterogeneities, implant geometric perturbations, and changes in source orientations, is encouraged in the dosimetric evaluation. The clinical workflow, logistics, and precautions are also presented.

Tumor-targeted pH-low insertion peptide delivery of theranostic gadolinium nanoparticles for image-guided nanoparticle-enhanced radiation therapy.

Tumor targeting studies using metallic nanoparticles (NPs) have shown that the enhanced permeability and retention effect may not be sufficient to deliver the amount of intratumoral and intracellular NPs needed for effective in vivo radiosensitization. This work describes a pH-Low Insertion Peptide (pHLIP) targeted theranostic agent to enable image-guided NP-enhanced radiotherapy using a clinically feasible amount of injected NPs. Conventional gadolinium (Gd) NPs were conjugated to pHLIPs and evaluated in vitro for radiosensitivity and in vivo for mouse MRI. Cultured A549 human lung cancer cells were incubated with 0.5 mM of pHLIP-GdNP or conventional GdNP. Mass spectrometry showed 78-fold more cellular Gd uptake with pHLIP-GdNPs, and clonogenic survival assays showed 44% more enhanced radiosensitivity by 5 Gy irradiation with pHLIP-GdNPs at pH 6.2. In contrast to conventional GdNPs, MR imaging of tumor-bearing mice showed pHLIP-GdNPs had a long retention time in the tumor (>9 h), suitable for radiotherapy, and penetrated into the poorly-vascularized tumor core. The Gd-enhanced tumor corresponded with low-pH areas also independently measured by an in vivo molecular MRI technique. pHLIPs actively target cell surface acidity from tumor cell metabolism and deliver GdNPs into cells in solid tumors. Intracellular delivery enhances the effect of short-range radiosensitizing photoelectrons and Auger electrons. Because acidity is a general hallmark of tumor cells, the delivery is more general than antibody targeting. Imaging the in vivo NP biodistribution and more acidic (often more aggressive) tumors has the potential for quantitative radiotherapy treatment planning and pre-selecting patients who will likely benefit more from NP radiation enhancement.

Adaptive Imaging Versus Periodic Surveillance for Intrafraction Motion Management During Prostate Cancer Radiotherapy.

OBJECTIVE: To evaluate the benefits of adaptive imaging with automatic correction compared to periodic surveillance strategies with either manual or automatic correction. METHODS: Using Calypso trajectories from 54 patients with prostate cancer at 2 institutions, we simulated 5-field intensity-modulated radiation therapy and dual-arc volumetric-modulated arc therapy with periodic imaging at various frequencies and with continuous adaptive imaging, respectively. With manual/automatic correction, we assumed there was a 30/1 second delay after imaging to determine and apply couch shift. For adaptive imaging, real-time "dose-free" cine-MV images during beam delivery are used in conjunction with online-updated motion pattern information to estimate 3D displacement. Simultaneous MV-kV imaging is only used to confirm the estimated overthreshold motion and calculate couch shift, hence very low additional patient dose from kV imaging. RESULTS: Without intrafraction intervention, the prostates could on average have moved out of a 3-mm margin for ∼20% of the beam-on time after setup imaging in current clinical situation. If the time interval from the setup imaging to beam-on can be reduced to only 30 seconds, the mean over-3 mm percentage can be reduced to ∼7%. For intensity-modulated radiation therapy simulation, with manual correction, 110 and 70 seconds imaging periods both reduced the mean over-3 mm time to ∼4%. Automatic correction could give another 1% to 2% improvement. However, with either manual or automatic correction, the maximum patient-specific over-3 mm time was still relatively high (from 6.4% to 12.6%) and those patients are actually clinically most important. In contrast, adaptive imaging with automatic intervention significantly reduced the mean percentage to 0.6% and the maximum to 2.7% and averagely only ∼1 kV image and ∼1 couch shift were needed per fraction. The results of volumetric-modulated arc therapy simulation show a similar trend to that of intensity-modulated radiation therapy. CONCLUSIONS: Adaptive continuous monitoring with automatic motion compensation is more beneficial than periodic imaging surveillance at similar or even less imaging dose.

High-dose-rate brachytherapy as monotherapy for prostate cancer: The impact of cellular repair and source decay.

PURPOSE: This work quantifies the influence of intrafraction DNA damage repair and cellular repopulation on biologically effective dose (BED) in Ir-192 high-dose-rate brachytherapy for prostate cancer. In addition, it examines the effect of source-decay-induced BED variation for patients treated at different time points in a source exchange cycle. MATERIALS AND METHODS: Current fractionation schemes are based on simplified-form BED = nd(1 + d/(α/ß)), which assumes that intrafraction repair, interfraction repair, and repopulation are negligible. We took accepted radiobiological parameters of Tk, Tp, and α from the recommendations of the AAPM TG-137, and recalculated the full-form BED. Fraction times were normalized to require 15 min for 20 Gy at 10 Ci. Calculations were carried out for both α/ß = 1.5 and 3 Gy. RESULTS: After accounting for intrafraction repair, interfraction repair, and/or repopulation, full-form BED calculations showed significant values, as compared with simplified-form BED. For 1-fraction 20 Gy fractionation, the full-form BED was only 64-82% of the simplified-form BED. Dose protraction effects were milder for smaller prescriptions (6 Gy/Fx), where full form was 87-94%. With regard to source decay, BED varied >20% for patients treated at the beginning and the end of a source exchange cycle for 20 Gy single-fraction prescription. CONCLUSIONS: Repair and repopulation can be significant in monotherapy high-dose-rate for prostate cancer. As fractionation schemes are established, the simplified BED calculation may not be appropriate. Investigators should consider evaluating BED as a range rather than a discrete value when presenting results unless source activity is explicitly incorporated as well.

Novel Eye Plaque Designs for Brachytherapy of Iris and Ciliary Body Melanoma and the First Clinical Application.

BACKGROUND: While traditional eye plaque brachytherapy can be used for the treatment of iris melanoma, it faces challenges of poor patient tolerability due to cornea-plaque touch caused by radius of curvature mismatch and potential dosimetric inaccuracy from incomplete coverage. We present novel plaque designs and the first clinical application of the plaques for iris melanoma. METHODS: Two dome-shaped plaques (EP2132 and EP1930) were designed to vault above the cornea to treat tumors of the iris and ciliary body. Image-based treatment planning of the first 2 clinical cases using the EP2132 plaque covered the tumor base plus a 2 mm margin and the involved ciliary body with at least 75 Gy to the tumor apex. RESULTS: The tumors decreased in size following treatment. The patients tolerated the treatment well. There was no adverse event associated with the traditional iris plaques, such as decreased vision, pain, corneal edema, glaucoma, or cataract. CONCLUSION: The novel dome-shaped plaques for the treatment of iris melanoma provide effective dose distribution, improved surgical maneuverability, and increased tolerability for the patient. This plaque model can be used to treat iris melanoma of various sizes, configurations, and locations, including the ciliary body. The need for a customized plaque platform for each patient is minimized.

Monte Carlo dosimetry modeling of focused kV x-ray radiotherapy of eye diseases with potential nanoparticle dose enhancement.

PURPOSE: Eye plaque brachytherapy is the most common approach for intraocular cancer treatment. It is, however, invasive and subject to large setup uncertainty due to the surgical operation. We propose a novel-focused kV x-ray technique with potential nanoparticle (NP) enhancement and evaluate its application in treating choroidal melanoma and iris melanoma by Monte Carlo (MC) dosimetry modeling. METHODS: A polycapillary x-ray lens was used to focus 45 kVp x rays to achieve pinpoint accuracy of dose delivery to small tumors near critical structures. In addition to allowing for beam focusing, the use of kV x rays takes advantage of the strong photoelectric absorption of metallic NPs in that energy regime and hence strong radiosensitization. We constructed an MC simulation program that takes into account the x-ray optic modeling and used GEANT4 for dosimetric calculation. Extensive phantom measurements using a prototype-focused x-ray system were carried out. The MC simulation of simple geometry phantom irradiation was first compared to measurements to verify the x-ray optic lens modeling in conjunction with the Geant4 dosimetric calculation. To simulate tumor treatment, a geometric eye model and two tumor models were constructed. Dose distributions of the simulated treatments were then calculated. NP radiosensitization was also simulated for two concentrations of 2 nm gold NP (AuNP) uniformly distributed in the tumor. RESULTS: The MC-simulated full width at half maximum (FWHM) and central-axis depth dose of the focused kV x-ray beam match those measured on EBT3 films within ~10% around the depth of focus of the beam. Dose distributions of the simulated ocular tumor treatments show that focused x-ray beams can concentrate the high-dose region in or close to the tumor plus margin. For the simulated posterior choroidal tumor treatment, with sufficient tumor coverage, the doses to the optic disc and fovea are substantially reduced with focused x-ray therapy compared to eye plaque treatment (3.8 vs 39.8 Gy and 11.1 vs 53.8 Gy, respectively). The eye plaque treatment was calculated using an Eye Physics plaque with I-125 seeds under TG43 assumption. For the energy spectrum used in this study, the average simulated dose enhancement ratios (DERs) are roughly 2.1 and 1.1 for 1.0% and 0.1% AuNP mass concentration in the tumor, respectively. CONCLUSION: Compared to eye plaque brachytherapy, the proposed focused kV x-ray technique is noninvasive and shows great advantage in sparing healthy critical organs without sacrificing the tumor control. The NP radiation dose enhancement is considerable at our proposed kV range even with a low NP concentration in the tumor, providing better critical structure protection and more flexibility for treatment planning.

On the use of bolus for pacemaker dose measurement and reduction in radiation therapy.

Special attention is required in planning and administering radiation therapy to patients with cardiac implantable electronic devices (CIEDs), such as pacemaker and defibrillator. The range of dose to CIEDs that can induce malfunction is large among CIEDs. Clinically significant defects have been reported at dose as low as 0.15 Gy. Therefore, accurate estimation of dose to CIED and dose reduction are both important even if the dose is expected to be less than the often-used 2-Gy limit. We investigated the use of bolus in in vivo dosimetry for CIEDs. Solid water phantom measurements of out-of-field dose for a 6-MV beam were performed using parallel plate chamber with and without 1- to 2-cm bolus covering the chamber. In vivo dosimetry at skin surface above the CIED was performed with and without bolus covering the CIED for three patients with the CIED <5 cm from the field edge. Chamber measured dose at depth ~0.5-1.5 cm below the skin surface, where the CIED is normally located, was reduced by ~7-48% with bolus. The dose reduction became smaller at deeper depths and with smaller field size. In vivo dosimetry at skin surface also indicated ~20%-60% lower dose when using bolus for the three patients. The dose measured with bolus more accurately reflects the dose to CIED and is less affected by contaminant electrons and linac head scatter. In general, the treatment planning system (TPS) calculation underestimated the dose to CIED, but it predicts the CIED dose more accurately when bolus is used. We recommend the use of 1- to 2-cm bolus to cover the CIED during in vivo CIED dose measurements for more accurate CIED dose estimation. If the CIED is placed <2 cm in depth and its dose is mainly from anterior beams, we recommend using the bolus during the entire course of radiation delivery to reduce the dose to CIED.

Incorporating patient-specific CT-based ophthalmic anatomy in modeling iodine-125 eye plaque brachytherapy dose distributions.

PURPOSE: To quantify the dosimetric impact of incorporating patient-specific CT-based models rather than the conventional stylized-standard model for eye plaque brachytherapy planning. METHODS AND MATERIALS: Plaque Simulator was used to plan 16 patients using both CT-based patient-specific eye model and stylized-standard (SS) eye models. Plaque position was initially based on the SS model and compared against their patient-specific model without changing the plaque loading pattern and seed strength. Dosimetric parameters were compared for tumor and healthy ocular structures. RESULTS: Patient-specific ocular parameters ranged from 0.40 to 1.38 of SS model values. If plaques were placed based on SS model eyelet positions, target volume receiving prescription dose (V100%) is overpredicted by 5.9% on average (max: 27%), and D95% is overpredicted by 17.2 Gy on average (max: 58.1 Gy). If the plaques were recentered, 13 of 16 patients had changes in V100% of less than 2%, whereas half of the patients still had optic disc dose difference greater than 5 Gy (max: 36.2 Gy). The largest differences were observed with a target-to-optic disk distance less than 6 mm. No substantial dose differences were observed for the tumor apex, fovea, lens, and opposing retina. CONCLUSIONS: Patient-specific modeling is recommended for clinical planning, especially with target-to-optic disk distances less than 6 mm, due to significant differences compared with SS model.

Supplement 2 for the 2004 update of the AAPM Task Group No. 43 Report: Joint recommendations by the AAPM and GEC-ESTRO.

Since the publication of the 2004 update to the American Association of Physicists in Medicine (AAPM) Task Group No. 43 Report (TG-43U1) and its 2007 supplement (TG-43U1S1), several new low-energy photon-emitting brachytherapy sources have become available. Many of these sources have satisfied the AAPM prerequisites for routine clinical purposes and are posted on the Brachytherapy Source Registry managed jointly by the AAPM and the Imaging and Radiation Oncology Core Houston Quality Assurance Center (IROC Houston). Given increasingly closer interactions among physicists in North America and Europe, the AAPM and the Groupe Européen de Curiethérapie-European Society for Radiotherapy & Oncology (GEC-ESTRO) have prepared another supplement containing recommended brachytherapy dosimetry parameters for eleven low-energy photon-emitting brachytherapy sources. The current report presents consensus datasets approved by the AAPM and GEC-ESTRO. The following sources are included: 125 I sources (BEBIG model I25.S17, BEBIG model I25.S17plus, BEBIG model I25.S18, Elekta model 130.002, Oncura model 9011, and Theragenics model AgX100); 103 Pd sources (CivaTech Oncology model CS10, IBt model 1031L, IBt model 1032P, and IsoAid model IAPd-103A); and 131 Cs (IsoRay Medical model CS-1 Rev2). Observations are included on the behavior of these dosimetry parameters as a function of radionuclide. Recommendations are presented on the selection of dosimetry parameters, such as from societal reports issuing consensus datasets (e.g., TG-43U1, AAPM Report #229), the joint AAPM/IROC Houston Registry, the GEC-ESTRO website, the Carleton University website, and those included in software releases from vendors of treatment planning systems. Aspects such as timeliness, maintenance, and rigor of these resources are discussed. Links to reference data are provided for radionuclides (radiation spectra and half-lives) and dose scoring materials (compositions and mass densities). The recent literature is examined on photon energy response corrections for thermoluminescent dosimetry of low-energy photon-emitting brachytherapy sources. Depending upon the dosimetry parameters currently used by individual physicists, use of these recommended consensus datasets may result in changes to patient dose calculations. These changes must be carefully evaluated and reviewed with the radiation oncologist prior to their implementation.

Comparison of 2D and 3D modeled tumor motion estimation/prediction for dynamic tumor tracking during arc radiotherapy.

Many real-time imaging techniques have been developed to localize a target in 3D space or in a 2D beam's eye view (BEV) plane for intrafraction motion tracking in radiation therapy. With tracking system latency, the 3D-modeled method is expected to be more accurate even in terms of 2D BEV tracking error. No quantitative analysis, however, has been reported. In this study, we simulated co-planar arc deliveries using respiratory motion data acquired from 42 patients to quantitatively compare the accuracy between 2D BEV and 3D-modeled tracking in arc therapy and to determine whether 3D information is needed for motion tracking. We used our previously developed low kV dose adaptive MV-kV imaging and motion compensation framework as a representative of 3D-modeled methods. It optimizes the balance between additional kV imaging dose and 3D tracking accuracy and solves the MLC blockage issue. With simulated Gaussian marker detection errors (zero mean and 0.39 mm standard deviation) and ~155/310/460 ms tracking system latencies, the mean percentage of time that the target moved >2 mm from the predicted 2D BEV position are 1.1%/4.0%/7.8% and 1.3%/5.8%/11.6% for the 3D-modeled and 2D-only tracking, respectively. The corresponding average BEV RMS errors are 0.67/0.90/1.13 mm and 0.79/1.10/1.37 mm. Compared to the 2D method, the 3D method reduced the average RMS unresolved motion along the beam direction from ~3 mm to ~1 mm, resulting in on average only <1% dosimetric advantage in the depth direction. Only for a small fraction of the patients, when tracking latency is long, the 3D-modeled method showed significant improvement of BEV tracking accuracy, indicating potential dosimetric advantage. However, if the tracking latency is short (~150 ms or less), those improvements are limited. Therefore, 2D BEV tracking has sufficient targeting accuracy for most clinical cases. The 3D technique is, however, still important in solving the MLC blockage problem during 2D BEV tracking.

Guidelines by the AAPM and GEC-ESTRO on the use of innovative brachytherapy devices and applications: Report of Task Group 167.

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used in the evaluation of innovative devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining the equivalence of the innovative treatment modality to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of innovative radiotherapy devices or applications is a critical part in which physicists should be actively involved. The physicist's role, along with physician colleagues, in this process is highlighted for innovative brachytherapy devices and applications and includes evaluation of (1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, (2) risks and benefits from a regulatory and safety perspective, and (3) resource assessment and preparedness. Further, it is suggested that any developed calibration methods be traceable to a primary standards dosimetry laboratory (PSDL) such as the National Institute of Standards and Technology in the U.S. or to other PSDLs located elsewhere such as in Europe. Clinical users should follow standards as approved by their country's regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the Accredited Dosimetry Calibration Laboratories in the U.S. is encouraged before a source is introduced into widespread routine clinical use. The American Association of Physicists in Medicine and the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) have developed guidelines for the safe and consistent application of brachytherapy using innovative devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. Nuclear Regulatory Commission, U.S. Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, U.S. Food and Drug Administration, European Commission for CE Marking (Conformité Européenne), and institutional review boards and radiation safety committees.

Concomitant Imaging Dose and Cancer Risk in Image Guided Thoracic Radiation Therapy.

PURPOSE: Kilovoltage cone beam computed tomography (CT) (kVCBCT) imaging guidance improves the accuracy of radiation therapy but imposes an extra radiation dose to cancer patients. This study aimed to investigate concomitant imaging dose and associated cancer risk in image guided thoracic radiation therapy. METHODS AND MATERIALS: The planning CT images and structure sets of 72 patients were converted to CT phantoms whose chest circumferences (Cchest) were calculated retrospectively. A low-dose thorax protocol on a Varian kVCBCT scanner was simulated by a validated Monte Carlo code. Computed doses to organs and cardiac substructures (for 5 selected patients of various dimensions) were regressed as empirical functions of Cchest, and associated cancer risk was calculated using the published models. The exposures to nonthoracic organs in children were also investigated. RESULTS: The structural mean doses decreased monotonically with increasing Cchest. For all 72 patients, the median doses to the heart, spinal cord, breasts, lungs, and involved chest were 1.68, 1.33, 1.64, 1.62, and 1.58 cGy/scan, respectively. Nonthoracic organs in children received 0.6 to 2.8 cGy/scan if they were directly irradiated. The mean doses to the descending aorta (1.43 ± 0.68 cGy), left atrium (1.55 ± 0.75 cGy), left ventricle (1.68 ± 0.81 cGy), and right ventricle (1.85 ± 0.84 cGy) were significantly different (P<.05) from the heart mean dose (1.73 ± 0.82 cGy). The blade shielding alleviated the exposure to nonthoracic organs in children by an order of magnitude. CONCLUSIONS: As functions of patient size, a series of models for personalized estimation of kVCBCT doses to thoracic organs and cardiac substructures have been proposed. Pediatric patients received much higher doses than did the adults, and some nonthoracic organs could be irradiated unexpectedly by the default scanning protocol. Increased cancer risks and disease adverse events in the thorax were strongly related to higher imaging doses and smaller chest dimensions.

AAPM and GEC-ESTRO guidelines for image-guided robotic brachytherapy: report of Task Group 192.

In the last decade, there have been significant developments into integration of robots and automation tools with brachytherapy delivery systems. These systems aim to improve the current paradigm by executing higher precision and accuracy in seed placement, improving calculation of optimal seed locations, minimizing surgical trauma, and reducing radiation exposure to medical staff. Most of the applications of this technology have been in the implantation of seeds in patients with early-stage prostate cancer. Nevertheless, the techniques apply to any clinical site where interstitial brachytherapy is appropriate. In consideration of the rapid developments in this area, the American Association of Physicists in Medicine (AAPM) commissioned Task Group 192 to review the state-of-the-art in the field of robotic interstitial brachytherapy. This is a joint Task Group with the Groupe Européen de Curiethérapie-European Society for Radiotherapy & Oncology (GEC-ESTRO). All developed and reported robotic brachytherapy systems were reviewed. Commissioning and quality assurance procedures for the safe and consistent use of these systems are also provided. Manual seed placement techniques with a rigid template have an estimated in vivo accuracy of 3-6 mm. In addition to the placement accuracy, factors such as tissue deformation, needle deviation, and edema may result in a delivered dose distribution that differs from the preimplant or intraoperative plan. However, real-time needle tracking and seed identification for dynamic updating of dosimetry may improve the quality of seed implantation. The AAPM and GEC-ESTRO recommend that robotic systems should demonstrate a spatial accuracy of seed placement ≤1.0 mm in a phantom. This recommendation is based on the current performance of existing robotic brachytherapy systems and propagation of uncertainties. During clinical commissioning, tests should be conducted to ensure that this level of accuracy is achieved. These tests should mimic the real operating procedure as closely as possible. Additional recommendations on robotic brachytherapy systems include display of the operational state; capability of manual override; documented policies for independent check and data verification; intuitive interface displaying the implantation plan and visualization of needle positions and seed locations relative to the target anatomy; needle insertion in a sequential order; robot-clinician and robot-patient interactions robustness, reliability, and safety while delivering the correct dose at the correct site for the correct patient; avoidance of excessive force on radioactive sources; delivery confirmation of the required number or position of seeds; incorporation of a collision avoidance system; system cleaning, decontamination, and sterilization procedures. These recommendations are applicable to end users and manufacturers of robotic brachytherapy systems.

Potential hazard due to induced radioactivity secondary to radiotherapy: the report of task group 136 of the American Association of Physicists in Medicine.

External-beam radiation therapy mostly uses high-energy photons (x-rays) produced by medical accelerators, but many facilities now use proton beams, and a few use fast-neutron beams. High-energy photons offer several advantages over lower-energy photons in terms of better dose distributions for deep-seated tumors, lower skin dose, less sensitivity to tissue heterogeneities, etc. However, for beams operating at or above 10 MV, some of the materials in the accelerator room and the radiotherapy patient become radioactive due primarily to photonuclear reactions and neutron capture, exposing therapy staff and patients to unwanted radiation dose. Some recent advances in radiotherapy technology require treatments using a higher number of monitor units and monitor-unit rates for the same delivered dose, and compared to the conventional treatment techniques and fractionation schemes, the activation dose to personnel can be substantially higher. Radiotherapy treatments with proton and neutron beams all result in activated materials in the treatment room. In this report, the authors review critically the published literature on radiation exposures from induced radioactivity in radiotherapy. They conclude that the additional exposure to the patient due to induced radioactivity is negligible compared to the overall radiation exposure as a part of the treatment. The additional exposure to the staff due to induced activity from photon beams is small at an estimated level of about 1 to 2 mSv y. This is well below the allowed occupational exposure limits. Therefore, the potential hazard to staff from induced radioactivity in the use of high-energy x-rays is considered to be low, and no specific actions are considered necessary or mandatory. However, in the spirit of the "As Low as Reasonably Achievable (ALARA)" program, some reasonable steps are recommended that can be taken to reduce this small exposure to an even lower level. The dose reduction strategies suggested should be followed only if these actions are considered reasonable and practical in the individual clinics. Therapists working with proton beam and neutron beam units handle treatment devices that do become radioactive, and they should wear extremity monitors and make handling apertures and boluses their last task upon entering the room following treatment. Personnel doses from neutron-beam units can approach regulatory limits depending on the number of patients and beams, and strategies to reduce doses should be followed.

A molecular dynamics simulation of DNA damage induction by ionizing radiation.

We present a multi-scale simulation of the early stage of DNA damages by the indirect action of hydroxyl ((•)OH) free radicals generated by electrons and protons. The computational method comprises of interfacing the Geant4-DNA Monte Carlo with ReaxFF molecular dynamics software. A clustering method was employed to map the coordinates of (•)OH-radicals extracted from the ionization-track-structures onto nano-meter simulation voxels filled with DNA and water molecules. The molecular dynamics simulation provides the time-evolution and chemical reactions in individual simulation voxels as well as the energy-landscape accounted for the DNA-(•)OH chemical reaction that is essential for the first-principle enumeration of hydrogen abstractions, chemical bond breaks, and DNA-lesions induced by collection of ions in clusters less than the critical dimension which is approximately 2-3 Å. We show that the formation of broken bonds leads to DNA-base and backbone damages that collectively propagate to DNA single and double-strand breaks. For illustration of the methodology, we focused on particles with an initial energy of 1 MeV. Our studies reveal a qualitative difference in DNA damage induced by low energy electrons and protons. Electrons mainly generate small pockets of (•)OH-radicals, randomly dispersed in the cell volume. In contrast, protons generate larger clusters along a straight-line parallel to the direction of the particle. The ratio of the total DNA double-strand breaks induced by a single proton and electron track is determined to be ≈4 in the linear scaling limit. In summary, we have developed a multi-scale computational model based on first-principles to study the interaction of ionizing radiation with DNA molecules. The main advantage of our hybrid Monte Carlo approach using Geant4-DNA and ReaxFF is the multi-scale simulation of the cascade of both physical and chemical events which result in the formation of biological damage. The tool developed in this work can be used in the future to investigate the relative biological effectiveness of light and heavy ions that are used in radiotherapy.

Real-time automatic fiducial marker tracking in low contrast cine-MV images.

PURPOSE: To develop a real-time automatic method for tracking implanted radiographic markers in low-contrast cine-MV patient images used in image-guided radiation therapy (IGRT). METHODS: Intrafraction motion tracking using radiotherapy beam-line MV images have gained some attention recently in IGRT because no additional imaging dose is introduced. However, MV images have much lower contrast than kV images, therefore a robust and automatic algorithm for marker detection in MV images is a prerequisite. Previous marker detection methods are all based on template matching or its derivatives. Template matching needs to match object shape that changes significantly for different implantation and projection angle. While these methods require a large number of templates to cover various situations, they are often forced to use a smaller number of templates to reduce the computation load because their methods all require exhaustive search in the region of interest. The authors solve this problem by synergetic use of modern but well-tested computer vision and artificial intelligence techniques; specifically the authors detect implanted markers utilizing discriminant analysis for initialization and use mean-shift feature space analysis for sequential tracking. This novel approach avoids exhaustive search by exploiting the temporal correlation between consecutive frames and makes it possible to perform more sophisticated detection at the beginning to improve the accuracy, followed by ultrafast sequential tracking after the initialization. The method was evaluated and validated using 1149 cine-MV images from two prostate IGRT patients and compared with manual marker detection results from six researchers. The average of the manual detection results is considered as the ground truth for comparisons. RESULTS: The average root-mean-square errors of our real-time automatic tracking method from the ground truth are 1.9 and 2.1 pixels for the two patients (0.26 mm/pixel). The standard deviations of the results from the 6 researchers are 2.3 and 2.6 pixels. The proposed framework takes about 128 ms to detect four markers in the first MV images and about 23 ms to track these markers in each of the subsequent images. CONCLUSIONS: The unified framework for tracking of multiple markers presented here can achieve marker detection accuracy similar to manual detection even in low-contrast cine-MV images. It can cope with shape deformations of fiducial markers at different gantry angles. The fast processing speed reduces the image processing portion of the system latency, therefore can improve the performance of real-time motion compensation.