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.

Review of clinical brachytherapy uncertainties: analysis guidelines of GEC-ESTRO and the AAPM.

BACKGROUND AND PURPOSE: A substantial reduction of uncertainties in clinical brachytherapy should result in improved outcome in terms of increased local control and reduced side effects. Types of uncertainties have to be identified, grouped, and quantified. METHODS: A detailed literature review was performed to identify uncertainty components and their relative importance to the combined overall uncertainty. RESULTS: Very few components (e.g., source strength and afterloader timer) are independent of clinical disease site and location of administered dose. While the influence of medium on dose calculation can be substantial for low energy sources or non-deeply seated implants, the influence of medium is of minor importance for high-energy sources in the pelvic region. The level of uncertainties due to target, organ, applicator, and/or source movement in relation to the geometry assumed for treatment planning is highly dependent on fractionation and the level of image guided adaptive treatment. Most studies to date report the results in a manner that allows no direct reproduction and further comparison with other studies. Often, no distinction is made between variations, uncertainties, and errors or mistakes. The literature review facilitated the drafting of recommendations for uniform uncertainty reporting in clinical BT, which are also provided. The recommended comprehensive uncertainty investigations are key to obtain a general impression of uncertainties, and may help to identify elements of the brachytherapy treatment process that need improvement in terms of diminishing their dosimetric uncertainties. It is recommended to present data on the analyzed parameters (distance shifts, volume changes, source or applicator position, etc.), and also their influence on absorbed dose for clinically-relevant dose parameters (e.g., target parameters such as D90 or OAR doses). Publications on brachytherapy should include a statement of total dose uncertainty for the entire treatment course, taking into account the fractionation schedule and level of image guidance for adaptation. CONCLUSIONS: This report on brachytherapy clinical uncertainties represents a working project developed by the Brachytherapy Physics Quality Assurances System (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this report has been reviewed and approved by the American Association of Physicists in Medicine.

Patient positioning based on a radioactive tracer implanted in patients with localized prostate cancer: a performance and safety evaluation.

PURPOSE: To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. METHODS AND MATERIALS: We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ((192)Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performed to test the positioning accuracy of the RealEye. RESULTS: The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). CONCLUSIONS: Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye.

A dosimetric uncertainty analysis for photon-emitting brachytherapy sources: report of AAPM Task Group No. 138 and GEC-ESTRO.

This report addresses uncertainties pertaining to brachytherapy single-source dosimetry preceding clinical use. The International Organization for Standardization (ISO) Guide to the Expression of Uncertainty in Measurement (GUM) and the National Institute of Standards and Technology (NIST) Technical Note 1297 are taken as reference standards for uncertainty formalism. Uncertainties in using detectors to measure or utilizing Monte Carlo methods to estimate brachytherapy dose distributions are provided with discussion of the components intrinsic to the overall dosimetric assessment. Uncertainties provided are based on published observations and cited when available. The uncertainty propagation from the primary calibration standard through transfer to the clinic for air-kerma strength is covered first. Uncertainties in each of the brachytherapy dosimetry parameters of the TG-43 formalism are then explored, ending with transfer to the clinic and recommended approaches. Dosimetric uncertainties during treatment delivery are considered briefly but are not included in the detailed analysis. For low- and high-energy brachytherapy sources of low dose rate and high dose rate, a combined dosimetric uncertainty <5% (k=1) is estimated, which is consistent with prior literature estimates. Recommendations are provided for clinical medical physicists, dosimetry investigators, and source and treatment planning system manufacturers. These recommendations include the use of the GUM and NIST reports, a requirement of constancy of manufacturer source design, dosimetry investigator guidelines, provision of the lowest uncertainty for patient treatment dosimetry, and the establishment of an action level based on dosimetric uncertainty. These recommendations reflect the guidance of the American Association of Physicists in Medicine (AAPM) and the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) for their members and may also be used as guidance to manufacturers and regulatory agencies in developing good manufacturing practices for sources used in routine clinical treatments.

Study of encapsulated 170Tm sources for their potential use in brachytherapy.

PURPOSE: High dose-rate (HDR) brachytherapy is currently performed with 192Ir sources, and 60Co has returned recently into clinical use as a source for this kind of cancer treatment. Both radionuclides have mean photon energies high enough to require specific shielded treatment rooms. In recent years, 169Yb has been explored as an alternative for HDR-brachytherapy implants. Although it has mean photon energy lower than 192Ir, it still requires extensive shielding to deliver treatment. An alternative radionuclide for brachytherapy is 170Tm (Z=69) because it has three physical properties adequate for clinical practice: (a) 128.6 day half-life, (b) high specific activity, and (c) mean photon energy of 66.39 keV. The main drawback of this radionuclide is the low photon yield (six photons per 100 electrons emitted). The purpose of this work is to study the dosimetric characteristics of this radionuclide for potential use in HDR-brachytherapy. METHODS: The authors have assumed a theoretical 170Tm cylindrical source encapsulated with stainless steel and typical dimensions taken from the currently available HDR 192Ir brachytherapy sources. The dose-rate distribution was calculated for this source using the GEANT4 Monte Carlo (MC) code considering both photon and electron 170Tm spectra. The AAPM TG-43 U1 brachytherapy dosimetry parameters were derived. To study general properties of 170Tm encapsulated sources, spherical sources encapsulated with stainless steel and platinum were also studied. Moreover, the influence of small variations in the active core and capsule dimensions on the dosimetric characteristics was assessed. Treatment times required for a 170Tm source were compared to those for 192Ir and 169Yb for the same contained activity. RESULTS: Due to the energetic beta spectrum and the large electron yield, the bremsstrahlung contribution to the dose was of the same order of magnitude as from the emitted gammas and characteristic x rays. Moreover, the electron spectrum contribution to the dose was significant up to 4 mm from the source center compared to the photon contribution. The dose-rate constant lamda of the cylindrical source was 1.23 cGy h(-1) U(-1). The behavior of the radial dose function showed promise for applications in brachytherapy. Due to the electron spectrum, the anisotropy was large for r <6 mm. Variations in manufacturing tolerances did not significantly influence the final dosimetry data when expressed in cGy h(-1) U(-1). For typical capsule dimensions, maximum reference dose rates of about 0.2, 10, and 2 Gy min(-1) would then be obtained for 170Tm, 192Ir, and 169Yb, respectively, resulting in treatment times greater than those for HDR 192Ir brachytherapy. CONCLUSIONS: The dosimetric characteristics of source designs exploiting the low photon energy of 170Tm were studied for potential application in HDR-brachytherapy. Dose-rate distributions were obtained for cylindrical and simplified spherical 170Tm source designs (stainless steel and platinum capsule materials) using MC calculations. Despite the high activity of 170Tm, calculated treatment times were much longer than for 192Ir.

A program for the independent verification of brachytherapy planning system calculations.

PURPOSE: In this work a spreadsheet based program is presented that to a large extent independently verifies the calculations of individual plans of brachytherapy treatment planning systems for low dose rate, high dose rate and pulsed dose rate techniques. MATERIAL AND METHODS: The verification program has been developed based on workbooks/spreadsheets. The treatment planning system output text files are automatically loaded into the new program, allowing the use of the source coordinates, the desired calculation point coordinates, and the dwell times of a patient plan. The source strength and the reference dates are entered by the user and then dose points calculations are independently performed. The program shows its results in a comparison of its calculated point dose data with the corresponding TPS outcome. RESULTS: Results of 250 clinical cases show agreement with the TPS outcome within a 2% level. CONCLUSIONS: The program allows the implementation of the recommendations to verify the clinical brachytherapy dosimetry in a simple and accurate way, in only few minutes and with a minimum of user interactions.

Patterns of care study for brachytherapy: results of the questionnaire for the years 2002 and 2007 in The Netherlands.

PURPOSE: The goal of the ESTRO Patterns of Care study for Brachytherapy in Europe (PCBE) 2002 was to develop an aid to analyse brachytherapy practices. A 2nd version of the PCB questionnaire was created for 2007. Data over 2007 were collected at the radiotherapy institutions in The Netherlands and compared with those from 2002. The aim of this study is to describe national brachytherapy practices, to demonstrate trends, and to provide data for rational health care planning. MATERIAL AND METHODS: Data were collected using a web-based questionnaire. For each centre, a local coordinator, responsible for coordinating the questionnaires and support of the further analysis was assigned. Data from the national cancer incidence registry was used for comparison with the data from the 21 Dutch departments. RESULTS: There was a decrease in low-dose rate equipment in parallel to an increase in both pulsed-dose rate and high-dose rate equipment. The use of 3D CT and MR based imaging techniques showed a slow rise. The most common clinical procedures were for prostate, gynaecological, and oesophageal tumours. A large increase (146%) in permanent implant prostate applications using 125I seeds was observed. The numbers of oesophageal and gynaecological treatments remained stable. There is concern on the low numbers of cases treated in some institutions for a few complex treatment sites. For head and neck, anal canal, paediatrics, bladder and eye interventions it ranged from 3-20 patients per year per institution. CONCLUSIONS: The increase in number of patient treated with brachytherapy is in accordance with the increases in cancer incidence. The percentage of all radiotherapy patients treated with brachytherapy (approximately 5%) remained stable. The survey identified certain trends in resources and techniques, as well as areas of expected improvement and possible gain in clinical outcome. Data reported from this survey can be used for further planning of resources, facilities and concentration of a low-volume specialised and complex treatments.

The evolution of brachytherapy treatment planning.

Brachytherapy is a mature treatment modality that has benefited from technological advances. Treatment planning has advanced from simple lookup tables to complex, computer-based dose-calculation algorithms. The current approach is based on the AAPM TG-43 formalism with recent advances in acquiring single-source dose distributions. However, this formalism has clinically relevant limitations for calculating patient dose. Dose-calculation algorithms are being developed based on Monte Carlo methods, collapsed cone, and solving the linear Boltzmann transport equation. In addition to improved dose-calculation tools, planning systems and brachytherapy treatment planning will account for material heterogeneities, scatter conditions, radiobiology, and image guidance. The AAPM, ESTRO, and other professional societies are working to coordinate clinical integration of these advancements. This Vision 20/20 article provides insight into these endeavors.

Development of a TLD mailed system for remote dosimetry audit for (192)Ir HDR and PDR sources.

BACKGROUND AND PURPOSE: In the framework of an ESTRO ESQUIRE project, the BRAPHYQS Physics Network and the EQUAL-ESTRO laboratory have developed a procedure for checking the absorbed dose to water in the vicinity of HDR or PDR sources using a mailed TLD system. The methodology and the materials used in the procedure are based on the existing EQUAL-ESTRO external radiotherapy dose checks. MATERIALS AND METHODS: A phantom for TLD postal dose assurance service, adapted to accept catheters from different HDR afterloaders, has been developed. The phantom consists of three PMMA tubes supporting catheters placed at 120 degrees around a central TLD holder. A study on the use of LiF powder type DTL 937 (Philitech) has been performed in order to establish the TLD calibration in dose-to-water at a given distance from (192)Ir source, as well as to determine all correction factors to convert the TLD reading into absorbed dose to water. The dosimetric audit is based on the comparison between the dose to water measured with the TL dosimeter and the dose calculated by the clinical TPS. Results of the audits are classified in four different levels depending on the ratio of the measured dose to the stated dose. The total uncertainty budget in the measurement of the absorbed dose to water using TLD near an (192)Ir HDR source, including TLD reading, correction factors and TLD calibration coefficient, is determined as 3.27% (1s). RESULTS: To validate the procedures, the external audit was first tested among the members of the BRAPHYQS Network. Since November 2004, the test has been made available for use by all European brachytherapy centres. To date, 11 centres have participated in the checks and the results obtained are very encouraging. Nevertheless, one error detected has shown the usefulness of this audit. CONCLUSION: A method of absorbed dose to water determination in the vicinity of an (192)Ir brachytherapy source was developed for the purpose of a mailed TL dosimetry system. The accuracy of the procedure was determined. This method allows a check of the whole dosimetry chain for this type of brachytherapy afterloading system and can easily be performed by mail to any institution in the European area and elsewhere. Such an external audit can be an efficient QC method complementary to internal quality control as it can reveal some errors which are not observable by other means.

Quality assurance in the EORTC randomized trial 22922/10925 investigating the role of irradiation of the internal mammary and medial supraclavicular lymph node chain works.

BACKGROUND AND PURPOSE: A quality assurance (QA) program in conjunction with the EORTC trial investigating the role of adjuvant internal mammary and medial supraclavicular irradiation in stage I-III breast cancer is presented. The results of a dummy run procedure and of an individual case review are compared to each other. The effects of recommendations based on QA procedures on the protocol compliance are evaluated. MATERIAL AND METHODS: Prior to protocol activation all participating institutes were asked to produce treatment plans according to the guidelines of the protocol based on manual outlines of an average patient. Thereafter, they were asked to provide data on each of their first six randomized patients. RESULTS: The dummy run provided a lot of information on specific treatment techniques. In the individual case review, additional patient- and tumor-related data were collected, showing the use of anatomic information for treatment planning. A comparison between both procedures revealed that the individual case reports concurred more accurately with protocol guidelines than the dummy run. CONCLUSION: It was observed that the number of systematic protocol deviations was substantially decreased in trial patients compared to the dummy run case. Therefore, it is concluded that this extensive QA program had a positive effect on the consistency of all institutes participating in the trial.

The EQUAL-ESTRO audit on geometric reconstruction techniques in brachytherapy.

BACKGROUND AND PURPOSE: A geometric check procedure of the reconstruction techniques used in brachytherapy treatment planning systems was developed by the EQUAL (European Quality Laboratory) Laboratory in the framework of the ESTRO's (European Society for Therapeutic Radiology and Oncology) project 'ESQUIRE' (Education Science and QUality assurance In Radiotherapy in Europe [Baumann M, Brada M. Towards equity in turbulent Europe ESTRO, European cooperation and the European Commission. Radiother Oncol 2005;75:251-2. Heeren G. The bright but ephemeral life of a rainbow. A chronical of seventeen years of intensive ESTRO-EU cooperation. Radiother Oncol 2005;75:253-7]) by the task group Braphyqs (Brachytherapy physics quality system). PATIENTS AND METHODS: The check is performed by using the so-called 'Baltas' phantom, mailed to the participating centres in order to check the local technique of geometric reconstruction used in dose calculation. RESULTS: To validate the procedures, the check was first tested among the members of the Braphyqs Network. Since November 2002, the system is open to other centres. Until now 152 reconstructions have been checked. Eighty-six percent of the results were within an acceptance level after the first check. For the remaining 14%, a second check has been proposed. The results of the re-checks are in most cases within an acceptance level, except for 2% of the reconstructions. CONCLUSIONS: The geometric check is available from the EQUAL Laboratory for all the brachytherapy centres. The decrease of the deviations observed between the two checks demonstrates the importance of this kind of external audit as some errors were revealed, which were not discovered before with techniques used in clinical quality control routines.

Quality control of brachytherapy equipment in the Netherlands and Belgium: current practice and minimum requirements.

BACKGROUND AND PURPOSE: Brachytherapy is applied in 39 radiotherapy institutions in The Netherlands and Belgium. Each institution has its own quality control (QC) programme to ensure safe and accurate dose delivery to the patient. The main goal of this work is to gain insight into the current practice of QC of brachytherapy in The Netherlands and Belgium and to reduce possible variations in test frequencies and tolerances by formulating a set of minimum QC-requirements. MATERIALS AND METHODS: An extensive questionnaire about QC of brachytherapy was distributed to and completed by the 39 radiotherapy institutions. A separate smaller questionnaire was sent to nine institutions performing intracoronary brachytherapy. The questions were related to safety systems, physical irradiation parameters and total time spent on QC. The results of the questionnaires were compared with recommendations given in international brachytherapy QC reports. RESULTS: The answers to the questionnaires showed large variations in test frequencies and test methods. Furthermore, large variations in time spent on QC exist, which is mainly due to differences in QC-philosophy and differences in the available resources. CONCLUSIONS: Based on the results of the questionnaires and the comparison with the international recommendations, a set of minimum requirements for QC of brachytherapy has been formulated. These guidelines will be implemented in the radiotherapy institutions in The Netherlands and Belgium.