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.

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.

Dosimetry of (125)I and (103)Pd COMS eye plaques for intraocular tumors: report of Task Group 129 by the AAPM and ABS.

Dosimetry of eye plaques for ocular tumors presents unique challenges in brachytherapy. The challenges in accurate dosimetry are in part related to the steep dose gradient in the tumor and critical structures that are within millimeters of radioactive sources. In most clinical applications, calculations of dose distributions around eye plaques assume a homogenous water medium and full scatter conditions. Recent Monte Carlo (MC)-based eye-plaque dosimetry simulations have demonstrated that the perturbation effects of heterogeneous materials in eye plaques, including the gold-alloy backing and Silastic insert, can be calculated with reasonable accuracy. Even additional levels of complexity introduced through the use of gold foil "seed-guides" and custom-designed plaques can be calculated accurately using modern MC techniques. Simulations accounting for the aforementioned complexities indicate dose discrepancies exceeding a factor of ten to selected critical structures compared to conventional dose calculations. Task Group 129 was formed to review the literature; re-examine the current dosimetry calculation formalism; and make recommendations for eye-plaque dosimetry, including evaluation of brachytherapy source dosimetry parameters and heterogeneity correction factors. A literature review identified modern assessments of dose calculations for Collaborative Ocular Melanoma Study (COMS) design plaques, including MC analyses and an intercomparison of treatment planning systems (TPS) detailing differences between homogeneous and heterogeneous plaque calculations using the American Association of Physicists in Medicine (AAPM) TG-43U1 brachytherapy dosimetry formalism and MC techniques. This review identified that a commonly used prescription dose of 85 Gy at 5 mm depth in homogeneous medium delivers about 75 Gy and 69 Gy at the same 5 mm depth for specific (125)I and (103)Pd sources, respectively, when accounting for COMS plaque heterogeneities. Thus, the adoption of heterogeneous dose calculation methods in clinical practice would result in dose differences >10% and warrant a careful evaluation of the corresponding changes in prescription doses. Doses to normal ocular structures vary with choice of radionuclide, plaque location, and prescription depth, such that further dosimetric evaluations of the adoption of MC-based dosimetry methods are needed. The AAPM and American Brachytherapy Society (ABS) recommend that clinical medical physicists should make concurrent estimates of heterogeneity-corrected delivered dose using the information in this report's tables to prepare for brachytherapy TPS that can account for material heterogeneities and for a transition to heterogeneity-corrected prescriptive goals. It is recommended that brachytherapy TPS vendors include material heterogeneity corrections in their systems and take steps to integrate planned plaque localization and image guidance. In the interim, before the availability of commercial MC-based brachytherapy TPS, it is recommended that clinical medical physicists use the line-source approximation in homogeneous water medium and the 2D AAPM TG-43U1 dosimetry formalism and brachytherapy source dosimetry parameter datasets for treatment planning calculations. Furthermore, this report includes quality management program recommendations for eye-plaque brachytherapy.

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.

Comparison of dose calculation methods for brachytherapy of intraocular tumors.

PURPOSE: To investigate dosimetric differences among several clinical treatment planning systems (TPS) and Monte Carlo (MC) codes for brachytherapy of intraocular tumors using 125I or 103Pd plaques, and to evaluate the impact on the prescription dose of the adoption of MC codes and certain versions of a TPS (Plaque Simulator with optional modules). METHODS: Three clinical brachytherapy TPS capable of intraocular brachytherapy treatment planning and two MC codes were compared. The TPS investigated were Pinnacle v8.0dp1, BrachyVision v8.1, and Plaque Simulator v5.3.9, all of which use the AAPM TG-43 formalism in water. The Plaque Simulator software can also handle some correction factors from MC simulations. The MC codes used are MCNP5 v1.40 and BrachyDose/EGSnrc. Using these TPS and MC codes, three types of calculations were performed: homogeneous medium with point sources (for the TPS only, using the 1D TG-43 dose calculation formalism); homogeneous medium with line sources (TPS with 2D TG-43 dose calculation formalism and MC codes); and plaque heterogeneity-corrected line sources (Plaque Simulator with modified 2D TG-43 dose calculation formalism and MC codes). Comparisons were made of doses calculated at points-of-interest on the plaque central-axis and at off-axis points of clinical interest within a standardized model of the right eye. RESULTS: For the homogeneous water medium case, agreement was within approximately 2% for the point- and line-source models when comparing between TPS and between TPS and MC codes, respectively. For the heterogeneous medium case, dose differences (as calculated using the MC codes and Plaque Simulator) differ by up to 37% on the central-axis in comparison to the homogeneous water calculations. A prescription dose of 85 Gy at 5 mm depth based on calculations in a homogeneous medium delivers 76 Gy and 67 Gy for specific 125I and 103Pd sources, respectively, when accounting for COMS-plaque heterogeneities. For off-axis points-of-interest, dose differences approached factors of 7 and 12 at some positions for 125I and 103Pd, respectively. There was good agreement (approximately 3%) among MC codes and Plaque Simulator results when appropriate parameters calculated using MC codes were input into Plaque Simulator. Plaque Simulator and MC users are perhaps at risk of overdosing patients up to 20% if heterogeneity corrections are used and the prescribed dose is not modified appropriately. CONCLUSIONS: Agreement within 2% was observed among conventional brachytherapy TPS and MC codes for intraocular brachytherapy dose calculations in a homogeneous water environment. In general, the magnitude of dose errors incurred by ignoring the effect of the plaque backing and Silastic insert (i.e., by using the TG-43 approach) increased with distance from the plaque's central-axis. Considering the presence of material heterogeneities in a typical eye plaque, the best method in this study for dose calculations is a verified MC simulation.

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.

Impact of source-production revision on the dose-rate constant of 131Cs interstitial brachytherapy sources.

PURPOSE: Since its introduction in 2004, the model CS-1 Rev.1 131Cs source has been used in many radiation therapy clinics for prostate brachytherapy. In 2006, this source model underwent a Rev.2 production revision. The aim of this work was to investigate the dosimetric influences of the Rev.2 production revision using high-resolution photon spectrometry. METHODS: Three CS-1 Rev.1 and three CS-1 Rev.2 131Cs sources were used in this study. The relative photon energy spectrum emitted by each source in the transverse bisector of the source was measured using a high-resolution germanium detector designed for low-energy photon spectrometry. Based on the measured photon energy spectrum and the radioactivity distribution in the source, the dose-rate constant (lamda) of each source was determined. The effects of the Rev.2 production revision were quantified by comparing the emitted photon energy spectra and the lamda values determined for the sources manufactured before and after the production revision. RESULTS: The relative photon energy spectrum originating from the principal emissions of 131Cs was found to be nearly identical before and after the Rev.2 revision. However, the portion of the spectrum originating from the production of fluorescent x rays in niobium, a trace element present in the source construction materials, was found to differ significantly between the Rev.1 and Rev.2 sources. The peak intensity of the Nb Kalpha and Nb Kbeta fluorescent x rays from the Rev.2 source was approximately 35% of that from the Rev.1 source. Consequently, the nominal lamda value of the Rev.2 source was found to be greater than that determined for the Rev.1 source by approximately 0.7% +/- 0.5%. CONCLUSIONS: A significant reduction (65%) in relative niobium fluorescent x-ray yield was observed in the Rev.2 131Cs sources. The impact of this reduction on the dose-rate constant was found to be small, with a relative difference of less than 1%. This study demonstrates that photon spectrometry can be used as a sensitive and convenient tool for monitoring and for quantifying the dosimetric effects of brachytherapy source-production revisions. Because production revision can change both the geometry and the atomic composition of brachytherapy sources, its dosimetric impact should be carefully monitored and evaluated for each production revision.

A photon spectrometric dose-rate constant determination for the Advantage Pd-103 brachytherapy source.

PURPOSE: Although several dosimetric characterizations using Monte Carlo simulation and thermoluminescent dosimetry (TLD) have been reported for the new Advantage Pd-103 source (IsoAid, LLC, Port Richey, FL), no AAPM consensus value has been established for the dosimetric parameters of the source. The aim of this work was to perform an additional dose-rate constant (lamda) determination using a recently established photon spectrometry technique (PST) that is independent of the published TLD and Monte Carlo techniques. METHODS: Three Model IAPD-103A Advantage Pd-103 sources were used in this study. The relative photon energy spectrum emitted by each source along the transverse axis was measured using a high-resolution germanium spectrometer designed for low-energy photons. For each source, the dose-rate constant was determined from its emitted energy spectrum. The PST-determined dose-rate constant (PST lamda) was then compared to those determined by TLD (TLD lamda) and Monte Carlo (MC lamda) techniques. A likely consensus lamda value was estimated as the arithmetic mean of the average lamda values determined by each of three different techniques. RESULTS: The average PST lamda value for the three Advantage sources was found to be (0.676 +.- 0.026) cGyh(-1) U(-1). Intersource variation in PST lamda was less than 0.01%. The PST lamda was within 2% of the reported MC lamda values determined by PTRAN, EGSnrc, and MCNP5 codes. It was 3.4% lower than the reported TLD lamda. A likely consensus lamda value was estimated to be (0.688 +/- 0.026) cGyh(-1) U(-1), similar to the AAPM consensus values recommended currently for the Theragenics (Buford, GA) Model 200 (0.686 +/- 0.033) cGyh(-1) U(-1), the NASI (Chatsworth, CA) Model MED3633 (0.688 +/- 0.033) cGyh(-1) U(-1), and the Best Medical (Springfield, VA) Model 2335 (0.685 +/- 0.033) cGyh(-1) U(-1) 103Pd sources. CONCLUSIONS: An independent lamda determination has been performed for the Advantage Pd-103 source. The PST lamda obtained in this work provides additional information needed for establishing a more accurate consensus lamda value for the Advantage Pd-103 source.

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.

Time dependence of energy spectra of brachytherapy sources and its impact on the half and the tenth value layers.

PURPOSE: Several factors including radionuclide purity influence the photon energy spectra from sealed brachytherapy sources. The existence of impurities and trace elements in radioactive materials as well as the substrate and encapsulation may not only alter the spectrum at a given time but also cause change in the spectra as a function of time. The purpose of this study is to utilize a semiempirical formalism, which quantitatively incorporates this time dependence, to calculate and evaluate the shielding requirement impacts introduced by this time dependence for a 103Pd source. METHODS: The formalism was used to calculate the NthVL thicknesses in lead for a 103Pd model 200 seed. Prior to 2005, the 103Pd in this source was purified to a level better than 0.006% of the total 103Pd activity, the key trace impurity consisting of 65Zn. Because 65Zn emits higher energy photons and has a much longer half-life of 244 days compared to 103Pd, its presence in 103Pd seeds led to a time dependence of the photon spectrum and other related physical quantities. This study focuses on the time dependence of the NthVL and the analysis of the corresponding shielding requirements. RESULTS: The results indicate that the first HVL and the first TVL in lead steadily increased with time for about 200 days and then reached a plateau. The increases at plateau were more than 1000 times compared to the corresponding values on the zeroth day. The second and third TVLs in lead reached their plateaus in about 100 and 60 days, respectively, and the increases were about 19 and 2.33 times the corresponding values on the zeroth day, respectively. All the TVLs demonstrated a similar time dependence pattern, with substantial increases and eventual approach to a plateau. CONCLUSIONS: The authors conclude that the time dependence of the emitted photon spectra from brachytherapy sources can introduce substantial variations in the values of the NthVL with time if certain impurities are present. The contribution of 65Zn to the dose rate constant was less than 0.03% in the earlier 103Pd seeds, and because of the use of new processing technologies since 2005, this impurity has been essentially eliminated, as demonstrated in the measured spectra of current 103Pd model 200 seeds. This study illustrates the importance of performing photon spectroscopy of the manufactured radioactive sources as a quality assurance test for an assessment over time of both the radiation protection and the dosimetric properties.

AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: report of Task Group 137.

During the past decade, permanent radioactive source implantation of the prostate has become the standard of care for selected prostate cancer patients, and the techniques for implantation have evolved in many different forms. Although most implants use 125I or 103Pd sources, clinical use of 131Cs sources has also recently been introduced. These sources produce different dose distributions and irradiate the tumors at different dose rates. Ultrasound was used originally to guide the planning and implantation of sources in the tumor. More recently, CT and/or MR are used routinely in many clinics for dose evaluation and planning. Several investigators reported that the tumor volumes and target volumes delineated from ultrasound, CT, and MR can vary substantially because of the inherent differences in these imaging modalities. It has also been reported that these volumes depend critically on the time of imaging after the implant. Many clinics, in particular those using intraoperative implantation, perform imaging only on the day of the implant. Because the effects of edema caused by surgical trauma can vary from one patient to another and resolve at different rates, the timing of imaging for dosimetry evaluation can have a profound effect on the dose reported (to have been delivered), i.e., for the same implant (same dose delivered), CT at different timing can yield different doses reported. Also, many different loading patterns and margins around the tumor volumes have been used, and these may lead to variations in the dose delivered. In this report, the current literature on these issues is reviewed, and the impact of these issues on the radiobiological response is estimated. The radiobiological models for the biological equivalent dose (BED) are reviewed. Starting with the BED model for acute single doses, the models for fractionated doses, continuous low-dose-rate irradiation, and both homogeneous and inhomogeneous dose distributions, as well as tumor cure probability models, are reviewed. Based on these developments in literature, the AAPM recommends guidelines for dose prescription from a physics perspective for routine patient treatment, clinical trials, and for treatment planning software developers. The authors continue to follow the current recommendations on using D90 and V100 as the primary quantitles, with more specific guidelines on the use of the imaging modalities and the timing of the imaging. The AAPM recommends that the postimplant evaluation should be performed at the optimum time for specific radionuclides. In addition, they encourage the use of a radiobiological model with a specific set of parameters to facilitate relative comparisons of treatment plans reported by different institutions using different loading patterns or radionuclides.

Clinical implementation of enhanced dynamic wedges into the Pinnacle treatment planning system: Monte Carlo validation and patient-specific QA.

The goal of this work is to present a systematic Monte Carlo validation study on the clinical implementation of the enhanced dynamic wedges (EDWs) into the Pinnacle(3) (Philips Medical Systems, Fitchburg, WI) treatment planning system (TPS) and QA procedures for patient plan verification treated with EDWs. Modeling of EDW beams in the Pinnacle(3) TPS, which employs a collapsed-cone convolution superposition (CCCS) dose model, was based on a combination of measured open-beam data and the 'Golden Segmented Treatment Table' (GSTT) provided by Varian for each photon beam energy. To validate EDW models, dose profiles of 6 and 10 MV photon beams from a Clinac 2100 C/D were measured in virtual water at depths from near-surface to 30 cm for a wide range of field sizes and wedge angles using the Profiler 2 (Sun Nuclear Corporation, Melbourne, FL) diode array system. The EDW output factors (EDWOFs) for square fields from 4 to 20 cm wide were measured in virtual water using a small-volume Farmer-type ionization chamber placed at a depth of 10 cm on the central axis. Furthermore, the 6 and 10 MV photon beams emerging from the treatment head of Clinac 2100 C/D were fully modeled and the central-axis depth doses, the off-axis dose profiles and the output factors in water for open and dynamically wedged fields were calculated using the Monte Carlo (MC) package EGS4. Our results have shown that (1) both the central-axis depth doses and the off-axis dose profiles of various EDWs computed with the CCCS dose model and MC simulations showed good agreement with the measurements to within 2%/2 mm; (2) measured EDWOFs used for monitor-unit calculation in Pinnacle(3) TPS agreed well with the CCCS and MC predictions within 2%; (3) all the EDW fields satisfied our validation criteria of 1% relative dose difference and 2 mm distance-to-agreement (DTA) with 99-100% passing rate in routine patient treatment plan verification using MapCheck 2D diode array.

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.

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.

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.

On the need to compensate for edema-induced dose reductions in preplanned (131)Cs prostate brachytherapy.

PURPOSE: Surgical trauma-induced edema and its protracted resolution can lead to significant dose reductions in preplanned (131)Cs prostate brachytherapy. The purpose of this work was to examine whether these dose reductions should be actively compensated for and to estimate the magnitude of the additional irradiation needed for dose compensation. METHODS AND MATERIALS: The quantitative edema resolution characteristics observed by Waterman et al. were used to examine the physical and radiobiologic effects of prostate edema in preplanned (131)Cs implants. The need for dose compensation was assessed using the dose responses observed in (125)I and (103)Pd prostate implants. The biologically effective dose, calculated with full consideration of edema evolution, was used to estimate the additional irradiation needed for dose compensation. RESULTS: We found that the edema-induced dose reduction in preplanned (131)Cs implants could easily exceed 10% of the prescription dose for implants with moderate or large edema. These dose reductions could lead to a >10% reduction in the biochemical recurrence-free survival for individual patients if the effect of edema was ignored. For a prescribed dose of 120 Gy, the number of 2-Gy external beam fractions needed to compensate for a 5%, 10%, 15%, 20%, and 25% edema-induced dose reduction would be one, four, six, seven, and nine, respectively, for prostate cancer with a median potential doubling time of 42 days. The required additional irradiation increased for fast-growing tumors and/or those less efficient in sublethal damage repair. CONCLUSION: Compensation of edema-induced dose reductions in preplanned (131)Cs prostate brachytherapy should be actively considered for those implants with moderate or large edema.

Photon energy spectrum emitted by a novel polymer-encapsulated 103Pd source and its effect on the dose rate constant.

Two independent groups have published intrinsic dosimetry parameters for the recently introduced OptiSeed103 interstitial brachytherapy source which contains 103Pd encapsulated by a novel polymer shell. The dose rate constant (Lambda) reported by the two groups, however, differed by more than 6% and there is currently no AAPM recommended consensus value for this source in clinical dosimetry. The aim of this work was to perform an independent determination of Lambda for the OptiSeed103 source using a recently developed photon spectrometry technique. Three OptiSeed103 sources (model 1032P) with known air-kerma strength were used in this study. The photon energy spectrum emitted along the radial direction on the source's bisector was measured in air using a high-resolution intrinsic germanium spectrometer designed and established for low-energy brachytherapy source spectrometry. The dose rate constant of each source was determined from its emitted energy spectrum and the spatial distribution of radioactivity in the source. Unlike other sources made with traditional titanium encapsulation, the photons emitted by the OptiSeed103 sources exhibited only slight spectral hardening, yielding a relative energy spectrum closer to that emitted by bare 103Pd. The dose rate constant determined by the photon spectrometry technique for water was 0.664 +/- 0.025 cGy h(-1) U(-1). This value agreed, within experimental uncertainties, with the Monte Carlo-calculated value (MCLambda) of 0.665 +/- 0.014 cGy h(-1) U(-1) and the TLD-measured value (with a Monte Carlo-calculated solid-phantom-to-water conversion factor) of 0.675 +/- 0.051 cGy h(-1) U(-1) reported by Wang and Hertel [Appl. Radiat. Isot. 63, 311-321 (2005)]. However, it differed by -6.7% from the McLambda of 0.712 +/- 0.043 cGy h(-1) U(-1) reported by Bernard and Vynckier [Phys. Med. Biol. 50, 1493-1504 (2005)]. The results obtained in this work provide additional information needed for establishing a consensus value for the dose rate constant for the OptiSeed103 source. It suggests that an eventual consensus value of Lambda for the OptiSeed103 source is likely to be closer to a value of 0.668 cGy h(-1) U(-1) rather than 0.693 cGy h(-1) U(-1) as initially recommended by the source manufacturer based on the two previously published results.

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.

Photon spectrometry for the determination of the dose-rate constant of low-energy photon-emitting brachytherapy sources.

Accurate determination of dose-rate constant (lambda) for interstitial brachytherapy sources emitting low-energy photons (< 50 keV) has remained a challenge in radiation dosimetry because of the lack of a suitable absolute dosimeter for accurate measurement of the dose rates near these sources. Indeed, a consensus value of lambda taken as the arithmetic mean of the dose-rate constants determined by different research groups and dosimetry techniques has to be used at present for each source model in order to minimize the uncertainties associated with individual determinations of lambda. Because the dosimetric properties of a source are fundamentally determined by the characteristics of the photons emitted by the source, a new technique based on photon spectrometry was developed in this work for the determination of dose-rate constant. The photon spectrometry technique utilized a high-resolution gamma-ray spectrometer to measure source-specific photon characteristics emitted by the low-energy sources and determine their dose-rate constants based on the measured photon-energy spectra and known dose-deposition properties of mono-energetic photons in water. This technique eliminates many of the difficulties arising from detector size, the energy dependence of detector sensitivity, and the use of non-water-equivalent solid phantoms in absolute dose rate measurements. It also circumvents the uncertainties that might be associated with the source modeling in Monte Carlo simulation techniques. It was shown that the estimated overall uncertainty of the photon spectrometry technique was less than 4%, which is significantly smaller than the reported 8-10% uncertainty associated with the current thermo-luminescent dosimetry technique. In addition, the photon spectrometry technique was found to be stable and quick in lambda determination after initial setup and calibration. A dose-rate constant can be determined in less than two hours for each source. These features make it ideal to determine the dose-rate constant of each source model from a larger and more representative sample of actual sources and to use it as a quality assurance resource for periodic monitoring of the constancy of lambda for brachytherapy sources used in patient treatments.