AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy.

The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for 192 Ir-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.

MaxiCalc: A tool for online dosimetric evaluation of source-tracking based treatment verification in HDR brachytherapy.

PURPOSE: Source tracking is becoming a more widely used approach in HDR brachytherapy treatment verification. While it provides a sensitive method to detect deviations from the treatment plan during delivery, it does not show the clinical significance of any detected changes. By incorporating a tool that calculates volumetric doses and DVH indices from measurements, source tracking systems can be expanded to assess dosimetric significance of any deviations from the plan. METHODS: The source tracking dose calculation tool, MaxiCalc, was developed in MATLAB. Validation was performed by comparing doses and DVH indices calculated in MaxiCalc to those calculated by the clinical TPS, for several test plans and 10 clinical plans. Clinical implementation was demonstrated by calculating volumetric doses from a clinical source tracking event. RESULTS: MaxiCalc showed excellent agreement with the clinical TPS for point and volumetric doses (mean difference < 0.01% and 0.1% respectively). MaxiCalc calculates dosimetrically equivalent plans to the TPS with agreement < 0.3% for all DVH indices except PTV V200%. Small differences seen for the clinical source tracking event were consistent with the known tracking uncertainties enabling them to be quantified for clinical decision making. Calculations are fast, enabling real-time use. CONCLUSIONS: MaxiCalc is an independent tool that calculates doses and DVH indices from dwells measured with any clinical HDR brachytherapy source tracking system. This extends the capabilities of source tracking systems from determining discrepancies in positions or times during delivery to assessing the dosimetric impact of any detected deviations, allowing for more comprehensive treatment verification and evaluation.

Coleus blumei viroid 7: a novel viroid resulting from genome recombination between Coleus blumei viroids 1 and 5.

The genus Coleviroid, family Pospiviroidae, comprises six known viroids, all infecting Plectranthus scutellarioides (Coleus blumei; coleus). In 2017, a novel viroid-like RNA sequence that shares ca. 65% identity with Coleus blumei viroid 1 (CbVd-1) was identified in a coleus cultivar infected by multiple coleviroids. Further sequence and secondary structure analyses are consistent with the discovery of a seventh viroid in the genus Coleviroid: tentatively named "Coleus blumei viroid 7" (CbVd-7). The viroid appears to be the product of a natural recombination event between CbVd-1 and Coleus blumei viroid 5. We prove CbVd-7 to be infectious and in turn demonstrate the ability of all known coleviroid left- and right-arm segments to recombine. With a length of 234 nucleotides, this is the smallest viroid described to date.

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy.

INTRODUCTION: In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients. METHODS: A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression. RESULTS: From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery. CONCLUSIONS: There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

HDR brachytherapy well chamber calibration and stability evaluated over twenty years of clinical use.

PURPOSE: The purpose of the study was to establish, using a retrospective analysis of existing hospital records, the long-term stability and accuracy of a high-dose-rate brachytherapy well chamber. This should be assessed to determine reliability and appropriate calibration frequency. The accrual of long-term data that demonstrates the stability of our chamber may inform others of the performance they might expect from similar equipment. METHODS AND MATERIALS: We evaluated air kerma strength measurements made with the PTW 32002 (Nucletron 077.091) high-dose-rate well chamber on 72 192Ir sources over an 18-year period and the seven calibrations of that chamber which span a 27-year period. RESULTS: Consecutive air kerma strength measurements agreed within 0.01% on average. The chamber measurement agreed with the source specification within 0.02% on average, but was up to 1.4% during some calibration periods. The chamber calibration coefficient varied by a maximum of 5% over seven chamber calibration measurements. CONCLUSIONS: The constancy of the well chamber current compared with the source manufacturer suggests that our chamber has been stable to better than 2% over a period of 18 years. Although the chamber has received different calibration coefficients over time, these coefficients are within the combined uncertainties of any two calibrations and are consistent with the chamber being stable. The agreement we have observed between clinical measurements and the source manufacturer would justify an action level for further investigation of 1%, for this specific chamber.

In vivo dosimetry in brachytherapy: Requirements and future directions for research, development, and clinical practice.

Brachytherapy can deliver high doses to the target while sparing healthy tissues due to its steep dose gradient leading to excellent clinical outcome. Treatment accuracy depends on several manual steps making brachytherapy susceptible to operational mistakes. Currently, treatment delivery verification is not routinely available and has led, in some cases, to systematic errors going unnoticed for years. The brachytherapy community promoted developments in in vivo dosimetry (IVD) through research groups and small companies. Although very few of the systems have been used clinically, it was demonstrated that the likelihood of detecting deviations from the treatment plan increases significantly with time-resolved methods. Time-resolved methods could interrupt a treatment avoiding gross errors which is not possible with time-integrated dosimetry. In addition, lower experimental uncertainties can be achieved by using source-tracking instead of direct dose measurements. However, the detector position in relation to the patient anatomy remains a main source of uncertainty. The next steps towards clinical implementation will require clinical trials and systematic reporting of errors and near-misses. It is of utmost importance for each IVD system that its sensitivity to different types of errors is well understood, so that end-users can select the most suitable method for their needs. This report aims to formulate requirements for the stakeholders (clinics, vendors, and researchers) to facilitate increased clinical use of IVD in brachytherapy. The report focuses on high dose-rate IVD in brachytherapy providing an overview and outlining the need for further development and research.

An integrated system for clinical treatment verification of HDR prostate brachytherapy combining source tracking with pretreatment imaging.

PURPOSE: High-dose-rate (HDR) prostate brachytherapy treatment is usually delivered in one or a few large dose fractions. Poor execution of a planned treatment could have significant clinical impact, as high doses are delivered in seconds, and mistakes in an individual fraction cannot be easily rectified. Given that most potential errors in HDR brachytherapy ultimately lead to a geographical miss, a more direct approach to verification of correct treatment delivery is to directly monitor the position of the source throughout the treatment. In this work, we report on the clinical implementation of our treatment verification system that uniquely combines the 2D source-tracking capability with 2D pretreatment imaging, using a single flat panel detector (FPD). METHODS AND MATERIALS: The clinical brachytherapy treatment couch was modified to allow integration of the FPD into the couch. This enabled the patient to be set up in the brachytherapy bunker in a position that closely matched that at treatment planning imaging. An anteroposterior image was acquired of the patient immediately before treatment delivery and was assessed by the Radiation Oncologist online, to reestablish the positions of the catheters relative to the prostate. Assessment of catheter positions was performed in the left-right and superior-inferior directions along the entire catheter length and throughout the treatment volume. Source tracking was then performed during treatment delivery, and the measured position of the source dwells were directly compared to the treatment plan for verification. RESULTS: The treatment verification system was integrated into the clinical environment without significant change to workflow. Two patient cases are presented in this work to provide clinical examples of this system, which is now in routine use for all patient treatments in our clinic. The catheter positions were visualized relative to the prostate, immediately before treatment delivery. For one of the patient cases presented in this work, they agreed with the treatment plan on average by 1.5 mm and were identifiable as a predominantly inferior shift. The source tracking was performed during treatment delivery, and for the same case, the mean deviation from the planned dwell positions was 1.9 mm (max = 4.9 mm) for 280 positions across all catheters. CONCLUSION: We have implemented our noninvasive treatment verification system based on an FPD in the clinical environment. The device is integrated into a patient treatment couch, and the process is now included in the routine clinical treatment procedure with minor impact on workflow. The system which combines both 2D pretreatment imaging and HDR 2D source tracking provides a range of information that can be used for comprehensive treatment verification. The system has the potential to meaningfully improve safety standards by allowing widespread adoption of routine treatment verification in HDR brachytherapy.

3D catheter reconstruction in HDR prostate brachytherapy for pre-treatment verification using a flat panel detector.

PURPOSE: High dose rate prostate brachytherapy is a widely-practiced treatment, delivering large conformal doses in relatively few treatment fractions. Inter- and intra-fraction catheter displacements have been reported. Unrecognized displacement can have a significant impact on dosimetry. Knowledge of the implant geometry at the time of treatment is important for ensuring safe and effective treatment. In this work we demonstrate a method to reconstruct the catheter positions pre-treatment, using a 'shift' imaging technique, and perform registration with the treatment plan for verification relative to the prostate. METHODS: Two oblique 'shift' images were acquired of a phantom containing brachytherapy catheters, representing the patient immediately pre-treatment. Using a back projection approach, the catheter paths were reconstructed in 3D and registered with the planned catheter paths. The robustness of the reconstruction and registration process was investigated as a function of phantom rotation. Catheter displacement detection was performed and compared to known applied displacements. RESULTS: Reconstruction of the implant geometry in 3D immediately prior to treatment was achieved. A mean reconstruction uncertainty of 0.8mm was determined for all catheters with a mean registration uncertainty of 0.5mm. A catheter displacement detection threshold of 2.2mm was demonstrated. Catheter displacements were all detected to within 0.5mm of the applied displacements. CONCLUSION: This technique is robust and sensitive to assess catheter displacements throughout the implant volume. This approach provides a method to detect, in 3D, changes in catheter positions relative to the prostate. The method has sufficient sensitivity to enable clinically significant decisions immediately prior to treatment delivery.

High dose rate brachytherapy source measurement intercomparison.

This work presents a comparison of air kerma rate (AKR) measurements performed by multiple radiotherapy centres for a single HDR 192Ir source. Two separate groups (consisting of 15 centres) performed AKR measurements at one of two host centres in Australia. Each group travelled to one of the host centres and measured the AKR of a single 192Ir source using their own equipment and local protocols. Results were compared to the 192Ir source calibration certificate provided by the manufacturer by means of a ratio of measured to certified AKR. The comparisons showed remarkably consistent results with the maximum deviation in measurement from the decay-corrected source certificate value being 1.1%. The maximum percentage difference between any two measurements was less than 2%. The comparisons demonstrated the consistency of well-chambers used for 192Ir AKR measurements in Australia, despite the lack of a local calibration service, and served as a valuable focal point for the exchange of ideas and dosimetry methods.

Activation of hip prostheses in high energy radiotherapy and resultant dose to nearby tissue.

High energy radiotherapy can produce contaminant neutrons through the photonuclear effect. Patients receiving external beam radiation therapy to the pelvis may have high-density hip prostheses. Metallic materials such as those in hip prostheses, often have high cross-sections for neutron interaction. In this study, Thackray (UK) prosthetic hips have been irradiated by 18 MV radiotherapy beams to evaluate the additional dose to patients from the activation products. Hips were irradiated in- and out-of field at various distances from the beam isocenter to assess activation caused in-field by photo-activation, and neutron activation which occurs both in and out-of-field. NaI(Tl) scintillator detectors were used to measure the subsequent gamma-ray emissions and their half-lives. High sensitivity Mg, Cu, P doped LiF thermoluminescence dosimeter chips (TLD-100H) were used to measure the subsequent dose at the surface of a prosthesis over the 12 h following an in-field irradiation of 10,000 MU to a hip prosthesis located at the beam isocenter in a water phantom. 53 Fe, 56 Mn, and 52 V were identified within the hip following irradiation by radiotherapy beams. The dose measured at the surface of a prosthesis following irradiation in a water phantom was 0.20 mGy over 12 h. The dose at the surface of prostheses irradiated to 200 MU was below the limit of detection (0.05 mGy) of the TLD100H. Prosthetic hips are activated by incident photons and neutrons in high energy radiotherapy, however, the dose resulting from activation is very small.

A method for verification of treatment delivery in HDR prostate brachytherapy using a flat panel detector for both imaging and source tracking.

PURPOSE: Verification of high dose rate (HDR) brachytherapy treatment delivery is an important step, but is generally difficult to achieve. A technique is required to monitor the treatment as it is delivered, allowing comparison with the treatment plan and error detection. In this work, we demonstrate a method for monitoring the treatment as it is delivered and directly comparing the delivered treatment with the treatment plan in the clinical workspace. This treatment verification system is based on a flat panel detector (FPD) used for both pre-treatment imaging and source tracking. METHODS: A phantom study was conducted to establish the resolution and precision of the system. A pretreatment radiograph of a phantom containing brachytherapy catheters is acquired and registration between the measurement and treatment planning system (TPS) is performed using implanted fiducial markers. The measured catheter paths immediately prior to treatment were then compared with the plan. During treatment delivery, the position of the (192)Ir source is determined at each dwell position by measuring the exit radiation with the FPD and directly compared to the planned source dwell positions. RESULTS: The registration between the two corresponding sets of fiducial markers in the TPS and radiograph yielded a registration error (residual) of 1.0 mm. The measured catheter paths agreed with the planned catheter paths on average to within 0.5 mm. The source positions measured with the FPD matched the planned source positions for all dwells on average within 0.6 mm (s.d. 0.3, min. 0.1, max. 1.4 mm). CONCLUSIONS: We have demonstrated a method for directly comparing the treatment plan with the delivered treatment that can be easily implemented in the clinical workspace. Pretreatment imaging was performed, enabling visualization of the implant before treatment delivery and identification of possible catheter displacement. Treatment delivery verification was performed by measuring the source position as each dwell was delivered. This approach using a FPD for imaging and source tracking provides a noninvasive method of acquiring extensive information for verification in HDR prostate brachytherapy.

A generic high-dose rate (192)Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism.

PURPOSE: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) (192)Ir source and a virtual water phantom were designed, which can be imported into a TPS. METHODS: A hypothetical, generic HDR (192)Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic (192)Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra(®) Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS™ ]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201)(3) voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR (192)Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by different investigators. MC results were then compared against dose calculated using TG-43 and MBDCA methods. RESULTS: TG-43 and PSS datasets were generated for the generic source, the PSS data for use with the ace algorithm. The dose-rate constant values obtained from seven MC simulations, performed independently using different codes, were in excellent agreement, yielding an average of 1.1109 ± 0.0004 cGy/(h U) (k = 1, Type A uncertainty). MC calculated dose-rate distributions for the two plans were also found to be in excellent agreement, with differences within type A uncertainties. Differences between commercial MBDCA and MC results were test, position, and calculation parameter dependent. On average, however, these differences were within 1% for ACUROS and 2% for ace at clinically relevant distances. CONCLUSIONS: A hypothetical, generic HDR (192)Ir source was designed and implemented in two commercially available TPSs employing different MBDCAs. Reference dose distributions for this source were benchmarked and used for the evaluation of MBDCA calculations employing a virtual, cubic water phantom in the form of a CT DICOM image series. The implementation of a generic source of identical design in all TPSs using MBDCAs is an important step toward supporting univocal commissioning procedures and direct comparisons between TPSs.

The influence of the dwell time deviation constraint (DTDC) parameter on dosimetry with IPSA optimisation for HDR prostate brachytherapy.

To investigate how the dwell time deviation constraint (DTDC) parameter, applied to inverse planning by simulated annealing (IPSA) optimisation limits large dwell times from occurring in each catheter and to characterise the effect on the resulting dosimetry for prostate high dose rate (HDR) brachytherapy treatment plans. An unconstrained IPSA optimised treatment plan, using the Oncentra Brachytherapy treatment planning system (version 4.3, Nucletron an Elekta company, Elekta AB, Stockholm, Sweden), was generated for 20 consecutive HDR prostate brachytherapy patients, with the DTDC set to zero. Successive constrained optimisation plans were also created for each patient by increasing the DTDC parameter by 0.2, up to a maximum value of 1.0. We defined a "plan modulation index", to characterise the change of dwell time modulation as the DTDC parameter was increased. We calculated the dose volume histogram indices for the PTV (D90, V100, V150, V200%) and urethra (D10%) to characterise the effect on the resulting dosimetry. The average PTV D90% decreases as the DTDC is applied, on average by only 1.5 %, for a DTDC = 0.4. The measures of high dose regions in the PTV, V150 and V200%, increase on average by less than 5 and 2 % respectively. The net effect of DTDC on the modulation of dwell times has been characterised by the introduction of the plan modulation index. DTDC applied during IPSA optimisation of HDR prostate brachytherapy plans reduce the occurrence of large isolated dwell times within individual catheters. The mechanism by which DTDC works has been described and its effect on the modulation of dwell times has been characterised. The authors recommend using a DTDC parameter no greater than 0.4 to obtain a plan with dwell time modulation comparable to a geometric optimised plan. This yielded on average a 1.5 % decrease in PTV coverage and an acceptable increase in V150%, without compromising the urethral dose.

Comparison of IPSA and HIPO inverse planning optimization algorithms for prostate HDR brachytherapy.

Publications have reported the benefits of using high-dose-rate brachytherapy (HDRB) for the treatment of prostate cancer, since it provides similar biochemical control as other treatments while showing lowest long-term complications to the organs at risk (OAR). With the inclusion of anatomy-based inverse planning opti- mizers, HDRB has the advantage of potentially allowing dose escalation. Among the algorithms used, the Inverse Planning Simulated Annealing (IPSA) optimizer is widely employed since it provides adequate dose coverage, minimizing dose to the OAR, but it is known to generate large dwell times in particular positions of the catheter. As an alternative, the Hybrid Inverse treatment Planning Optimization (HIPO) algorithm was recently implemented in Oncentra Brachytherapy V. 4.3. The aim of this work was to compare, with the aid of radiobiological models, plans obtained with IPSA and HIPO to assess their use in our clinical practice. Thirty patients were calculated with IPSA and HIPO to achieve our department's clinical constraints. To evaluate their performance, dosimetric data were collected: Prostate PTV D90(%), V100(%), V150(%), and V200(%), Urethra D10(%), Rectum D2cc(%), and conformity indices. Additionally tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with the BioSuite software. The HIPO optimization was performed firstly with Prostate PTV (HIPOPTV) and then with Urethra as priority 1 (HIPOurethra). Initial optimization constraints were then modified to see the effects on dosimetric parameters, TCPs, and NTCPs. HIPO optimizations could reduce TCPs up to 10%-20% for all PTVs lower than 74 cm3. For the urethra, IPSA and HIPOurethra provided similar NTCPs for the majority of volume sizes, whereas HIPOPTV resulted in large NTCP values. These findings were in agreement with dosimetric values. By increasing the PTV maximum dose constraints for HIPOurethra plans, TCPs were found to be in agreement with IPSA without affecting the urethral NTCPs. 

A respiratory correlated image guided surgery method: quantitative accuracy results in swine and human cadaver environments.

BACKGROUND: Intervention on small targets in the lung is difficult, leading our team to develop a highly accurate respiratory correlated image guided surgery (RCIGS) system. METHODS: Simulated point source targets were implanted into ex vivo porcine and human cadaver lungs attached to a ventilator. The RCIGS system was utilized to guide intervention in the presence of respiratory motion using a commercially available electromagnetic tracking solution. After intervention, the lungs were imaged to determine the target registration error between the target and needle. RESULTS: The system tumor position modeling had sub-mm accuracy. The mean intervention error for 12 porcine targets was 3.8 mm. The mean target registration error on four targets in a human cadaver was 4.0 mm at a mean depth of 9 cm. CONCLUSIONS: The system provides an accuracy for intervention on targets of less than 1 cm in diameter at depths of up to 10 cm. A system of this accuracy outperforms current clinical standards.

The effects of metallic implants on electroporation therapies: feasibility of irreversible electroporation for brachytherapy salvage.

PURPOSE: Electroporation-based therapies deliver brief electric pulses into a targeted volume to destabilize cellular membranes. Nonthermal irreversible electroporation (IRE) provides focal ablation with effects dependent on the electric field distribution, which changes in heterogeneous environments. It should be determined if highly conductive metallic implants in targeted regions, such as radiotherapy brachytherapy seeds in prostate tissue, will alter treatment outcomes. Theoretical and experimental models determine the impact of prostate brachytherapy seeds on IRE treatments. MATERIALS AND METHODS: This study delivered IRE pulses in nonanimal, as well as in ex vivo and in vivo tissue, with and in the absence of expired radiotherapy seeds. Electrical current was measured and lesion dimensions were examined macroscopically and with magnetic resonance imaging. Finite-element treatment simulations predicted the effects of brachytherapy seeds in the targeted region on electrical current, electric field, and temperature distributions. RESULTS: There was no significant difference in electrical behavior in tissue containing a grid of expired radiotherapy seeds relative to those without seeds for nonanimal, ex vivo, and in vivo experiments (all p > 0.1). Numerical simulations predict no significant alteration of electric field or thermal effects (all p > 0.1). Histology showed cellular necrosis in the region near the electrodes and seeds within the ablation region; however, there were no seeds beyond the ablation margins. CONCLUSION: This study suggests that electroporation therapies can be implemented in regions containing small metallic implants without significant changes to electrical and thermal effects relative to use in tissue without the implants. This supports the ability to use IRE as a salvage therapy option for brachytherapy.

The correlation of tissue motion within the lung: implications on fiducial based treatments.

In radiation therapy many motion management and alignment techniques rely on the accuracy of an internal fiducial acting as a surrogate for target motion within the lung. Although fiducials are routinely used as surrogates for tumor motion, the extent to which varying spatial locations in the lung move similarly to other locations has yet to be quantitatively analyzed. In an attempt to analyze the motion correlation throughout the lung, ten primary lung cancer patients underwent IRB-approved 4DCT scans in the supine position. Deformable registration produced motion vectors for each voxel between exhalation and inhalation. Modeling was performed for each vector and all surrounding vectors within the lung in order to determine the mean 3D Euclidean distance necessary for an implanted fiducial to correlate with surrounding tissue motion to within 3 mm (left lower: 1.7 cm, left upper: 2.1 cm, right lower 1.6 cm, and right upper 2.9 cm). No general implantation rule of where to position a fiducial with respect to the tumor was found as the motion is highly patient and lobe specific. Correlation maps are presented showcasing spatial anisotropy of the motion of tissue surrounding the tumor.

A comparison of out-of-field dose and its constituent components for intensity-modulated radiation therapy versus conformal radiation therapy: implications for carcinogenesis.

PURPOSE: To investigate differences in scatter and leakage between 6-MV intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3DCRT); to describe the relative contributions of internal patient scatter, collimator scatter, and head leakage; and to discuss implications for second cancer induction. METHODS AND MATERIALS: Dose was measured at increasing distances from the field edge in a water bath with a sloping wall (1) under full scatter conditions, (2) with the field edge abutting but outside the bath to prevent internal (water) scatter, and (3) with the beam aperture plugged to reflect leakage only. RESULTS: Internal patient scatter from IMRT is 11% lower than 3DCRT, but collimator scatter and head leakage are five and three times higher, respectively. Ultimately, total scattered dose is 80% higher with IMRT; however this difference is small in absolute terms, being 0.14% of prescribed dose. Secondary dose from 3DCRT is mostly due to internal patient scatter, which contributes 70% of the total and predominates until 25 cm from the field edge. For IMRT, however, machine scatter/leakage is the dominant source, contributing 65% of the secondary dose. Internal scatter predominates for just the first 10 cm from field edge, collimator scatter for the next 10 cm, and head leakage thereafter. CONCLUSIONS: Out-of-field dose is 80% higher with IMRT, but differences are tiny in absolute terms. Reductions in internal patient scatter with IMRT are outweighed by increased machine scatter and leakage, at least for small fields. Reductions from IMRT in dose to tissues within the portals and in internal scatter, which predominates close to the field edge, means that calculations based solely on dose to distant tissues may overestimate carcinogenic risks.