International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Physics Contribution
Global Harmonization of Quality Assurance Naming Conventions in Radiation Therapy Clinical Trials Christos Melidis, MSc,* Walther R. Bosch, DSc,y Joanna Izewska, PhD,z Elena Fidarova, MD,x Eduardo Zubizarreta, MD,x Kenneth Ulin, PhD,jj Satoshi Ishikura, MD,{ David Followill, Medical Physicist (Prof),# James Galvin, Medical Physicist (PhD),** Annette Haworth, Medical Physicist (Prof),yy Deidre Besuijen, MSc,zz Clark H. Clark, PhD,xx Elizabeth Miles, MSc,jjjj Edwin Aird, PhD,jjjj Damien C. Weber,{{ Coen W. Hurkmans, PhD,## and Dirk Verellen, Medical Physicist (Prof)*** *European Organization for the Research and Treatment of CancereRadiation Oncology Group (EORTC-ROG), Radiation Therapy Quality Assurance (RTQA), Brussels, Belgium; yWashington University, representing Advanced Technology Consortium, Radiation Oncology, St. Louis, Missouri; z Dosimetry Laboratory and xApplied Radiation Biology and Radiotherapy Section, International Atomic Energy Agency, Vienna, Austria; jjDepartment of Radiation Oncology, University of Massachusetts Medical School, Representing Quality Assurance Review Center, Worcester, Massachusetts; {Department of Radiation Oncology, Juntendo University, Representing Japan Clinical Oncology Group, RTQA, Tokyo, Japan; #Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Representing Radiological Physics Center, RTQA, Houston, Texas; **Department of Radiation Oncology, Thomas Jefferson University, Representing Radiation Therapy Oncology Group, RTQA, Philadelphia, Pennsylvania; yyDepartment of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, representing TransTasman Radiation Oncology Group (TROG) Cancer Research, Newcastle, Australia; zzNorth West Cancer Centre, Representing TROG Cancer Research, Newcastle, Australia; xxDepartment of Medical Physics, St. Luke’s Cancer Centre, Royal
Reprint requests to: Christos Melidis, MSc, European Organization for Research and Treatment of Cancer, Ave E. Mounier 83, 1200 Brussels, Belgium. Tel: (þ32) 27-74-15 07; E-mail: [email protected] This publication was supported by Fonds Cancer, Belgium. The steering committee members of the Global Clinical Trials RTQA Harmonization Group in May 2014 are as follows. International: The International Atomic Energy Agency; North America: Imaging and Radiation Oncology Core, National Cancer Institute of Canada Clinical Trials Group, and Radiation Therapy Oncology Group; Europe: European Organization for the Research and Treatment of CancereRadiation Oncology Int J Radiation Oncol Biol Phys, Vol. 90, No. 5, pp. 1242e1249, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.08.348
Group, Radiotherapy Trials Quality Assurance; Asia: Japan Clinical Oncology Group; Australia: TransTasman Radiation Oncology Group. Conflict of interest: none. AcknowledgmentsdThe authors would like to thank other active participants in the formation of the Global Clinical Trials RTQA Harmonization Group not listed as authors above: Australia: Tomas Kron, Martin Ebert, and Joan Hatton; Belgium: Akos Gulyban; Canada: Coreen Corning; Switzerland: Stefano Gianolini; United States: Jeff Michalski, Geoff Ibbott, Vikram Bhadrasain, Andrea Molineau, William Straube, and Ying Xiao.
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Surrey County Hospital, Guildford, Surrey and National Physical Laboratory, Teddington, Middlesex, representing Radiation Therapy Trials Quality Assurance (RTTQA), United Kingdom; jjjjMount Vernon Cancer Centre, Northwood, Middlesex representing RTTQA, United Kingdom; {{Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland, Representing the EORTC-ROG, RTQA, Brussels, Belgium; ##Catharina Hospital, Eindhoven, The Netherlands, Representing EORTC-ROG, RTQA, Brussels, Belgium; and ***Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium Received Jun 17, 2014, and in revised form Aug 5, 2014. Accepted for publication Aug 28, 2014.
Summary Various radiation therapy quality assurance (RTQA) procedures and naming conventions are used by clinical trial groups worldwide. The Global Harmonisation Group here presents an overview of these procedures and names and a new harmonized RTQA naming convention for use in clinical trials incorporating RT. This overview, incorporating the harmonization of RTQA naming conventions from 27 to 10, will facilitate intergroup trial collaboration and simplify exchange and interpretation of RTQA results.
Purpose: To review the various radiation therapy quality assurance (RTQA) procedures used by the Global Clinical Trials RTQA Harmonization Group (GHG) steering committee members and present the harmonized RTQA naming conventions by amalgamating procedures with similar objectives. Methods and Materials: A survey of the GHG steering committee members’ RTQA procedures, their goals, and naming conventions was conducted. The RTQA procedures were classified as baseline, preaccrual, and prospective/retrospective data capture and analysis. After all the procedures were accumulated and described, extensive discussions took place to come to harmonized RTQA procedures and names. Results: The RTQA procedures implemented within a trial by the GHG steering committee members vary in quantity, timing, name, and compliance criteria. The procedures of each member are based on perceived chances of noncompliance, so that the quality of radiation therapy planning and treatment does not negatively influence the trial measured outcomes. A comparison of these procedures demonstrated similarities among the goals of the various methods, but the naming given to each differed. After thorough discussions, the GHG steering committee members amalgamated the 27 RTQA procedures to 10 harmonized ones with corresponding names: facility questionnaire, beam output audit, benchmark case, dummy run, complex treatment dosimetry check, virtual phantom, individual case review, review of patients’ treatment records, and protocol compliance and dosimetry site visit. Conclusions: Harmonized RTQA harmonized naming conventions, which can be used in all future clinical trials involving radiation therapy, have been established. Harmonized procedures will facilitate future intergroup trial collaboration and help to ensure comparable RTQA between international trials, which enables meta-analyses and reduces RTQA workload for intergroup studies. Ó 2014 Elsevier Inc.
Introduction The Global Clinical Trials Quality Assurance of Radiation Therapy Harmonization Group (GHG) (1) includes representation from clinical trial quality assurance (QA) offices from around the world (www.RTQAHarmonisation.org). The GHG’s main objective is to harmonize and improve the radiation therapy (RT) QA within multi-institutional cooperative clinical trials for the treatment of cancer (2). The steering committee members at present are detailed in the first-page footnote. All organizations and cooperative groups participating in the GHG ensure the quality of RT through their own established QA procedures, with some originating more than 40 years ago (3). Further information on the GHG can be found at the group’s website. There are some distinct variations within and between each group’s RTQA procedures found in the literature
(4-6), and this often complicates intergroup trial cooperation. For some intergroup trials, the RTQA is performed through adaption to one of the participating groups’ RTQA procedures, whereas in other trials each group follows its own procedures. For example, within the EORTC 10853Ductal Carcinoma In-Situ (DCIS) intergroup trial (7), the RTQA is centrally performed by EORTC-ROG using their RTQA infrastructure. Similarly, the patient-specific RTQA of the new joint Radiation Therapy Oncology Group (RTOG) 0848-EORTC 40084 trial is performed through infrastructure made available by RTOG. On the other hand, the RTQA within the Supremo trial (8) is performed by several RTQA groups (RTTQA, EORTC, and TransTasman Radiation Oncology Group [TROG]). Although these examples show that intergroup trial cooperation is already possible, the absence of harmonized procedures made the initiation of RTQA within these trials more labor intensive and complicated than needed. Additionally,
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coordination of RTQA activities, as well as RTQA data analysis and interpretation, is hampered by the lack of harmonized procedures. Additionally, for sites recruiting to a variety of clinical trial groups, the investigator site often needs to perform similar tasks for each separate trial group. Furthermore, meta-analyses of RTQA clinical trial data are now hindered by the large variety in RTQA procedures, which renders any meaningful intercomparison difficult. The purpose of this study was to review the various definitions and naming conventions of the RTQA procedures as defined in the RT section (or separate RT Planning and Delivery Guideline document) of each trial protocol used by each steering committee member’s organization within RT clinical trials. Given the observed similarities concerning the goals of the various globally implemented RTQA procedures within the GHG, a new harmonized set of RTQA procedures and corresponding naming conventions is presented.
accrue patients: export and upload a complete RT dataset into the GHG member’s reviewing software, adhere to the structure delineation and RT planning requirements of the protocol, or plan and deliver a specified dose using an advanced RT technique.
Methods and Materials A survey of the RTQA procedures of each GHG steering committee member was conducted. The results are presented in Table 1 and the definitions follow below.
Baseline For a site to participate in a clinical trial with RT, it must first become a participant within the QA program of a GHG member. Baseline QA procedures ensure that sites can meet minimum established requirements for trial participation as required by the GHG member.
Facility and basic dosimetric requirements Facility questionnaire The facility questionnaire collects information about the site’s contact personnel, workload, and RT and QA equipment and procedures. It ensures that minimum requirements established by the requesting GHG member (eg the maximum number of patients per specialist per year, available QA equipment) are met (9). Beam output audit/external reference dosimetry audit/ reference beam output This procedure is a verification of the dose delivery under reference conditions at the site. It is a dose measurement performed by a national or international auditor, independent from the site, and must meet specific requirements established by the requesting GHG member (10, 11). Variations exist among the GHG steering committee members concerning the measurement detector, geometry, frequency, number of beams, and RT machines to be evaluated.
Preaccrual Trial-specific preaccrual procedures verify that sites can meet any combination of the following before they begin to
Protocol-compliant dummy patient or site connectivity check Completing a test case is a common RTQA procedure. Quantifying the degree of variation from the protocol can determine the level of “education” or intervention required before trial accrual begins. A major deviation is a “significant” variation from the protocol that may affect the validity of interpretation of trial results, would this test case be an actual trial patient, whereas minor deviations may require education to prevent major deviations in actual trial patients (12). As an example, the nondelineation or not-accurate delineation of an organ at risk (OAR) may be considered a minor deviation, whereas the same observation on the margins between clinical and planned target volume may be considered a major deviation. Benchmark case by Radiological Physics Center (RPC) and TROG/dry run by Image-guided Therapy QA Center (ATC-ITC)/dummy run by EORTC-ROG, Japan Clinical Oncology Group (JCOG), and RTOG/outlining and planning cases/exercises by Radiation Therapy Trials Quality Assurance (RTTQA) Sites are required to contour and/or plan on a common set of CT datasets (which provides an opportunity to quantify contouring and planning variations between sites) according to the protocol and then successfully transmit the plan electronically to the GHG member. The procedure is sometimes split into 2 steps: a delineation exercise on a common set of CT datasets, and then a planning exercise on precontoured CT datasets (13, 14). Any variation is given as feedback to the site (with potential resubmission), so that protocol compliance will be improved during patient accrual. These procedures also test the clarity and feasibility of the RT instructions within the RT and RTQA section of a protocol and the RTQA guidelines before patient accrual begins and may lead to their further refinement. Benchmark case by EORTC-ROG and International Atomic Energy Agency (IAEA)/rapid review by RPC, RTOG, and ATC-ITC/pretrial case review by RTTQA/dummy run by TROG Sites are required to submit a protocol-compliant treatment plan on an in-house, nontrial patient with similar trial pathology. The dataset is checked for its integrity, delineation, and dose constraint compliance, and any variation is given as feedback to the site (with potential resubmission), to improve protocol agreement during patient accrual.
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RTQA procedures among the GHG steering committee members Baseline
Member ATC-ITC
Facility and basic dosimetric requirements Not performed
Prospective/retrospective RTQA data capture and analysis
Preaccrual Protocol-compliant dummy patient or site connectivity check Data submission test or rapid review or dry run
Advanced RT technique credentialing Not performed
Remote review of patients’ RT treatments
Site visits
Not performed 1. Basic archiving 2. 1 þ completeness check 3. 2 þ compute DVHs 4. 3 þ reconcile structures 5. 4 þ image registration and case report forms
EORTC-ROG Facility questionnaire and external reference dosimetry audit by RPC or other QA office IAEA Facility questionnaire and reference beam output JCOG Facility questionnaire and external reference dosimetry audit RPC Facility questionnaire and OSLD/TLD beam output audit
Dummy run or Complex dosimetry digital data integrity check or virtual quality assurance phantom procedure
Individual case review Not and case report forms performed
Benchmark cases
Individual case review Not and case report forms performed Individual case review Not and case report forms performed
RTOG
Facility questionnaire and external reference dosimetry audit by RPC
Dummy run or rapid review or dry run
RTTQA
Facility questionnaire and external reference dosimetry audit by RTTQA or IPEM/NPL*
TROG
Facility questionnaire and external reference dosimetry audit (eg, ARPANSA/ACDS)
Outlining and planning cases/exercises or pretrial case review Benchmark cases or dummy run or digital data integrity quality assurance
Dummy run or digital data integrity quality assurance Benchmark cases or rapid review
Complex dosimetry check Complex dosimetry check
Credentialing for Review of patients’ advanced technology treatment records, clinical trials or timely reviews, complex dosimetry and case report check forms Credentialing for Individual case review advanced and case report technology forms clinical trials Credentialing for advanced techniques
Individual case review and case report forms/plan assessment form
Credentialing for advanced technology clinical trials
Individual case review and case report forms
On-site dosimetry review visits On-site dosimetry review visits by RPC On-site dosimetry visit
On-site dosimetry review visits by TROG (or approved service)
Abbreviations: ATC Z Advanced Technology Consortium; ARPANSA/ACDS Z Australian Radiation Protection and Nuclear Safety Agency/ Australian Clinical Dosimetry Service; EORTC-ROG Z European Organization for the Research and Treatment of CancereRadiation Oncology Group; GHG Z Global Clinical Trials RTQA Harmonization Group; IAEA Z International Atomic Energy Agency; IPEM/NPL Z Institute of Physics and Engineering in Medicine/National Physical Laboratory; ITCZ Image-guided Therapy QA Center; JCOG Z Japan Clinical Oncology Group; OSLD/ TLD Z optically stimulated/thermoluminescent dosimeter; RPC Z Radiological Physics Center; RTOG Z Radiation Therapy Oncology Group; RTQA Z Radiation Therapy Quality Assurance; RTTQA Z Radiation Therapy Trials Quality Assurance; TROG Z TransTasman Radiation Oncology Group.
Data submission test by ATC-ITC/dry run by RTOG/ digital data integrity quality assurance by EORTC-ROG, JCOG, and TROG A site is required to upload an in-house patient’s RT dataset that was planned using the same treatment technique and equipment to be used for patients within the
trial, including complete datasets from any imaging modalities and/or cone-beam CT. The dataset is checked for its integrity and anonymity of patient details, verifying that a site can export and upload the required datasets, so that prospective reviews meet protocol time frames.
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Advanced RT technique credentialing
reviewing a combination of diagnostic images and RT target volume and OAR structure sets and treatment plans or conducting site visits. Here again a major deviation is the same as under “Protocol-compliant dummy patient” (12).
The purpose of this credentialing is to increase the likelihood that sites have the “necessary expertise and resources” to safely implement new irradiation techniques, such as intensity modulated RT, volumetric modulated arc therapy, and Tomotherapy, in the context of a clinical trial (15). Currently there exist variations among the GHG members concerning the appropriate detectors, acceptable dose limits, frequency, and auditing bodies (3, 16). Complex dosimetry check (CDC) This end-to-end test uses a mailed phantom for planning CT acquisition, treatment planning, and dose delivery verification. The absolute doses between calculation and measurement must agree within predefined limits as set by the GHG member, and the dose is measured in at least 1 plane. The dosimeters are provided by the auditing organization and may include, for example, ion chambers, films, thermoluminescent dosimeters (TLDs), and optically stimulated luminescence dosimeters (OSLDs)/TLDs. Credentialing for advanced techniques by RTTQA and TROG This credentialing includes questionnaires and a process document (description and examples of all relevant procedures in recruiting site), verification of electronic transfer of data, outlining exercises, planning exercises, and dose point and distribution measurements on phantoms for both standard and clinical trial plans (16-20). This procedure is accomplished during site visits. Credentialing for advanced technology clinical trials by RPC and RTOG This procedure is accomplished either via a benchmark treatment plan or simulation, planning, and irradiation of an anthropomorphic phantom and includes the components of CDC, with the addition of questionnaires, a dosimetry review, and a review of the site’s QA, dosimetry procedures and records. Virtual phantom Sites use a provided CT dataset to plan a treatment according to specific guidelines. The plan is recalculated on the sites’ own QA phantom geometry, and the phantom is irradiated according to plan, avoiding the necessity of a phantom to be mailed to the site. The dataset and the required measurement files are uploaded to the EORTC for evaluation (21).
Prospective/retrospective RTQA data capture and analysis These procedures assure that the protocol requirements are being or have been followed for on-trial patients by
Remote review of patients’ RT treatments Timely review by RPC/individual case review by EORTCROG, IAEA, JCOG, RTOG, RTTQA, and TROG/image registration by ITC Timely review consists of review of the actual delineation and treatment plan of trial patients, including diagnostic images if applicable, to assess target volumes and OARs or repositioning. Where image-guided RT is used, organ motion and treatment response images may also be collected. This procedure assures protocol compliance of trial patients and can be done prospectively (22) or retrospectively (5, 23-25). Prospective review provides an opportunity for protocol compliance feedback to the site, such that delineation and planning changes can be made before the patient begins treatment. Prospective feedback reduces protocol deviations, creating stronger statistical significance for the results of the trial (22). Retrospective reviews that are fed back to the site during trial accrual may also have a positive impact on protocol compliance, but only for subsequent patients. When referring to the image registration procedure by ITC, it presupposes the previous use of “Basic Archiving,” “Completeness Check,” “Compute DoseeVolume Histograms,” and “Reconcile Structures.” Table 1 presents these last 4 procedures under ITC only: (1) Basic Archiving: Storing of patients’ RT datasets for possible future evaluation; (2) Completeness Check: Identical to data submission test but using trial patient datasets instead of “dummy patients”; (3) Compute DoseeVolume Histograms: A doseonly constraints protocol compliance check; (4) Reconcile Structures: A target volume and OAR delineation and dose constraints protocol compliance check. Review of patient’s treatment record by RPC Treatment plans are reviewed retrospectively to ensure that they have met the dosimetric and delineation requirements of the protocol. Measurements made at the site through the OSLD/TLD Beam Output Audit program and on-site dosimetry review visits (see below) are used, combined with the treatment parameters provided by the site (eg field size, depth, monitor unit [MU] setting), to independently verify the dose received by the patient. Case report forms/plan assessment form Sites retrospectively send paper or electronic reports concerning the RT treatment for all trial patients. The questions are predefined and usually include details of prescribed and delivered irradiations, as well as volume sizes and dose distribution to them. Although some of this information can be extracted from the review of the RT plan, this only represents what was planned for the patient. Efforts are already being
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conducted by the National Cancer Institute of the United States towards the global harmonization of case report forms (26).
Site visits On-site dosimetry visit by RTTQA This is a visit that ensures consistency between predicted and measured dose and includes measurements of output in reference conditions, as well as credentialing for advanced techniques using a protocol-compliant plan on a phantom. On-site dosimetry review visit by TROG A trial QA representative reviews the trial protocol with personnel from the site and observes the entire treatment process for a trial patient to confirm that the institution has properly implemented the protocol and to check for any protocol ambiguities. The procedure also includes measurements of output in reference conditions, as well as dose points and dose distributions using phantoms. On-site dosimetry review visit by RPC This consists of a review of the site’s treatment planning dosimetry data used to calculate beam-on time for each trial patient, the QA procedures and documentation, a review of treatment records to ascertain the consistency of the procedures used for treatment planning and MU calculations, and also includes dosimetry measurements.
Results The RTQA required within a clinical trial is based on the RT section of each trial protocol. Because RTQA’s mission is to ensure RT protocol compliance of all participating sites, the RT section must be comprehensive, be clear, and identify the RTQA required. A reason for the existence of differences in procedures among the GHG members may be the nonstandardization of the RT protocol section (27). The GHG steering committee members strive to reduce RT protocol noncompliance in delineation, planning, and treatment delivery through their individually established RTQA procedures. The procedures follow good clinical practice and international standards; however, they differ in quantity, timing, title, and compliance criteria. The baseline RTQA procedures between the RTQA groups are the same for each trial and participating site, whereas the preaccrual and prospective/retrospective data capture and analysis procedures vary per RTQA group and per trial (Table 1), depending among others on the influence that the RT component may have on the trial’s main question and the level of RT technique complexity that is allowed or in question. The main differences between the procedures implemented by the various RTQA groups are detailed below: Baseline: No real differences exist, besides the different minimum requirements established per the GHG steering committee members.
Harmonization of RTQA naming conventions 1247
Protocol-compliant dummy patient or site connectivity check: There are differences in the depth of procedures, depending on the complexity of the trial and the relevance of RT to the trial’s question. Some of the procedures only check the site’s connectivity abilities, whereas others also check the protocol compliance on a “dummy patient.” Advanced RT technique credentialing: Complex dosimetry check and credentialing for advanced techniques by RTTQA and TROG use a physical phantom and dosimeters, both provided by the auditing body. Credentialing for advanced technology clinical trials by RPC and RTOG can be accomplished using in-house equipment, whereas virtual phantom procedure by EORTC-ROG is always accomplished using in-house equipment. The RTTQA, TROG, RPC, and RTOG procedures have an augmented workload, with the parallel hope of strengthening the participants’ knowledge and ability to participate in the trial. Remote review of patients’ RT treatments: All but one of the procedures review the trial patients’ delineations and RT plan prospectively, during patient treatment, or retrospectively, whereas review of patient’s treatment record by RPC also acts as an independent MU calculation procedure but is only carried out retrospectively. Site visits: Whereas RTTQA’s procedure consists of measurements of output in reference conditions and credentialing for advanced techniques, TROG and RPC procedures also observe the entire treatment process, also performing phantom measurements using a protocolcompliant plan. In addition to that, RPC’s procedure consists of MU calculations for all trial patients. An in-depth reading of the definition of each procedure shows that more than half of the 27 procedures have common goals but are labelled differently, whereas 4 of them are prerequisites to others. Using this information the GHG steering committee members have harmonized the RTQA naming conventions, reducing their number from 27 to 10 (Table 2). The new RTQA procedures are as follows: Facility questionnaire: Demographics, workload, and QA equipment and procedures of the site. Beam output audit: Beam output measurement under reference conditions. Benchmark case: Planning and/or delineation test on a common CT dataset. Dummy run (with or without delineation exercise): Using imaging data of an in-house patient, this procedure is either a protocol compliance treatment plan test or a simple connectivity check. Complex treatment dosimetry check: Dosimetric test of advanced treatment techniques using a phantom provided by the GHG member or approved external dosimetry audit group. Virtual phantom: dosimetric test of advanced treatment techniques using in-house phantom.
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Naming conventions of RTQA procedures of the GHG steering committee members
Naming convention categories Baseline
Preaccrual
Prospective/retrospective RTQA data capture and analysis
Current name
New name
Facility questionnaire External reference dosimetry audit OSLD/TLD beam output audit Reference beam output Benchmark case by RPC and TROG Dry run by ITC Dummy run by EORTC-ROG, JCOG, and RTOG Outlining and planning cases/exercises by RTTQA Digital data integrity quality assurance Dry run by RTOG Data submission test Benchmark case by EORTC-ROG, IAEA Dummy run by TROG Pretrial case review Rapid review Credentialing for advanced technology clinical trials Complex dosimetry check Credentialing for advanced techniques Virtual phantom procedure Image registration by Advanced Technology Consortium (having completeness check, basic archiving, compute doseevolume histograms, and reconcile structures as prerequisites) Individual case review Timely review Review of patients’ treatment records Case report forms On-site dosimetry review visit by RPC On-site dosimetry review visit by TROG On-site dosimetry visit
Facility questionnaire Beam output audit
Benchmark case
Dummy run (without delineation exercise)
Dummy run (with delineation exercise)
Complex treatment dosimetry check
Virtual phantom (Prospective or retrospective) individual case review
Review of patients’ treatment records Case report forms Protocol compliance and dosimetry site visit
Abbreviations as in Table 1.
(Prospective or retrospective) individual case review: Review of the actual treatment plan and delineation of trial patients. Review of patients’ treatment records: Retrospective review of the actual treatment plan and delineation of trial patients, combined with measurements and protocol compliance and dosimetry site visits. Case report forms: Review of retrospectively submitted forms by each site on all trial patients concerning their RT treatment. Protocol compliance and dosimetry site visit: Beam output audit and complex treatment dosimetry check. It may also include observations of the entire treatment process for a trial patient, trial patients’ MU calculations, local QA procedures, and documentation and review of treatment records.
Discussion This article presented the various RTQA procedures used by the GHG steering committee members. Several
differences were found concerning similar procedures. As an example, the frequency and number of beams to be analyzed in the beam output audit varies greatly, with RPC and RTOG asking for every machine and energy on a yearly basis, and EORTC-ROG asking for the lowest and highest energy every other year. Furthermore, IAEA uses TLDs, RPC, RTOG, and EORTC-ROG use OSLD/TLDs, and in other groups ion chambers or alanine would be acceptable. In addition, the acceptable limits differ, with EORTC-ROG and IAEA requiring results within 5% and RPC and RTOG asking for 3%. Another example is the different reviewing software used among the GHG steering committee members, as well as the analysis methods, dosimeters, phantom designs, and acceptable limits used for the complex treatment dosimetry check. Such different compliance criteria can be seen, for example, when comparing the RPC procedure with the RTTQA one, with the procedure compliance criteria for g analysis ranging from 7%/4 mm to 3%/ 3 mm, respectively (3, 16). The GHG has identified all these differences and is working toward their harmonization, keeping in mind the need to apply different trialspecific criteria.
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As yet there is no consensus regarding which RTQA procedures should be used per trial. Whereas for some trials a limited QA program is performed, for others very extensive tests are conducted. It might be worthwhile to investigate what the optimal combination for both high trial compliance and cost-effectiveness of RTQA procedures could be for a given trial on the basis of the trial specifics, like the trial’s main question, the complexity of the RT given, and the design of the study (28). This requires further research into the effectiveness of the various procedures and their combination (29). Out of the analysis of the 27 procedures that were identified among the GHG steering committee members, a harmonized set of 10 procedures was formulated to be used in all future RT clinical trials.
Harmonization of RTQA naming conventions 1249
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15. 16. 17.
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within multicentre clinical trials? Eur J Cancer 2012;48:32323239. Clark CH, Miles EA, Urbano MT, et al. Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer. Br J Radiol 2009;82:585-594. Followill DS, Urie M, Galvin JM, et al. Credentialing for participation in clinical trials. Front Oncol 2012;2:198. Clark CH, Hansen VN, Chantler H, et al. Dosimetry audit for a multicentre IMRT head and neck trial. Radiother Oncol 2009;93:102-108. Miles E, Venables K. Radiotherapy quality assurance: facilitation of radiotherapy research and implementation of technology. Clin Oncol (R Coll Radiol) 2012;24:710-712. Kron T, Pham D, Roxby P, et al. Credentialing of radiotherapy centres for a clinical trial of adaptive radiotherapy for bladder cancer (TROG 10.01). Radiother Oncol 2012;103:293-298. Kron T, Willis D, Bignell F, et al. Centre credentialing for Trans Tasman Radiation Oncology Group trial 06.02: Multicentre feasibility study of accelerated partial breast irradiation. J Med Imaging Radiat Oncol 2009;53:412-418. Middleton M, Frantzis J, Healy B, et al. Successful implementation of image-guided radiation therapy quality assurance in the Trans Tasman Radiation Oncology Group 08.01 PROFIT Study. Int J Radiat Oncol Biol Phys 2011;81:1576-1581. Weber DC, Vallet V, Molineu A, et al. IMRT credentialing for prospective trials using institutional virtual phantoms: results of a joint European Organization for the Research and Treatment of Cancer and Radiological Physics Center project. Radiat Oncol 2014;9:123. Coskun M, Straube W, Hurkmans C. Quality Assurance of Radiotherapy in the Ongoing EORTC 22042-26042 Trial for Atypical and Malignant Meningioma: Results from the Dummy Run and Prospective Individual Case Review. Submitted to Eur J Cancer 2012. Peters LJ, O’Sullivan B, Giralt J, et al. Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: Results from TROG 02.02. J Clin Oncol 2010;28:2996-3001. Abrams RA, Winter KA, Regine WF, et al. Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704da phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 2012; 82:809-816. Rosenblatt E, Jones G, Sur RK, et al. Adding external beam to intraluminal brachytherapy improves palliation in obstructive squamous cell oesophageal cancer: A prospective multi-centre randomized trial of the International Atomic Energy Agency. Radiother Oncol 2010;97: 488-494. NCI. CRF Harmonization and Standardization. Available at: https://wiki. nci.nih.gov/display/CRF/CRFþHarmonizationþandþStandardization. Accessed December 31, 2013. Fairchild A, Bar-Deroma R, Collette L, et al. Development of clinical trial protocols involving advanced radiation therapy techniques: The European Organisation for Research and Treatment of Cancer Radiation Oncology Group approach. Eur J Cancer 2012;48:10481054. Weber DC, Hurkmans CW, Melidis C, et al. Outcome impact and costeffectiveness of quality assurance for radiotherapy planned for the EORTC 22071-24071 prospective study for head and neck cancer. Radiother Oncol 2014. Bekelman JE, Deye JA, Vikram B, et al. Redesigning radiotherapy quality assurance: Opportunities to develop an efficient, evidencebased system to support clinical trialsdreport of the National Cancer Institute Work Group on Radiotherapy Quality Assurance. Int J Radiat Oncol Biol Phys 2012;83:782-790.
Radiation Oncology biology
physics
www.redjournal.org
Physics Contribution
Global Harmonization of Quality Assurance Naming Conventions in Radiation Therapy Clinical Trials Christos Melidis, MSc,* Walther R. Bosch, DSc,y Joanna Izewska, PhD,z Elena Fidarova, MD,x Eduardo Zubizarreta, MD,x Kenneth Ulin, PhD,jj Satoshi Ishikura, MD,{ David Followill, Medical Physicist (Prof),# James Galvin, Medical Physicist (PhD),** Annette Haworth, Medical Physicist (Prof),yy Deidre Besuijen, MSc,zz Clark H. Clark, PhD,xx Elizabeth Miles, MSc,jjjj Edwin Aird, PhD,jjjj Damien C. Weber,{{ Coen W. Hurkmans, PhD,## and Dirk Verellen, Medical Physicist (Prof)*** *European Organization for the Research and Treatment of CancereRadiation Oncology Group (EORTC-ROG), Radiation Therapy Quality Assurance (RTQA), Brussels, Belgium; yWashington University, representing Advanced Technology Consortium, Radiation Oncology, St. Louis, Missouri; z Dosimetry Laboratory and xApplied Radiation Biology and Radiotherapy Section, International Atomic Energy Agency, Vienna, Austria; jjDepartment of Radiation Oncology, University of Massachusetts Medical School, Representing Quality Assurance Review Center, Worcester, Massachusetts; {Department of Radiation Oncology, Juntendo University, Representing Japan Clinical Oncology Group, RTQA, Tokyo, Japan; #Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Representing Radiological Physics Center, RTQA, Houston, Texas; **Department of Radiation Oncology, Thomas Jefferson University, Representing Radiation Therapy Oncology Group, RTQA, Philadelphia, Pennsylvania; yyDepartment of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, representing TransTasman Radiation Oncology Group (TROG) Cancer Research, Newcastle, Australia; zzNorth West Cancer Centre, Representing TROG Cancer Research, Newcastle, Australia; xxDepartment of Medical Physics, St. Luke’s Cancer Centre, Royal
Reprint requests to: Christos Melidis, MSc, European Organization for Research and Treatment of Cancer, Ave E. Mounier 83, 1200 Brussels, Belgium. Tel: (þ32) 27-74-15 07; E-mail: [email protected] This publication was supported by Fonds Cancer, Belgium. The steering committee members of the Global Clinical Trials RTQA Harmonization Group in May 2014 are as follows. International: The International Atomic Energy Agency; North America: Imaging and Radiation Oncology Core, National Cancer Institute of Canada Clinical Trials Group, and Radiation Therapy Oncology Group; Europe: European Organization for the Research and Treatment of CancereRadiation Oncology Int J Radiation Oncol Biol Phys, Vol. 90, No. 5, pp. 1242e1249, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.08.348
Group, Radiotherapy Trials Quality Assurance; Asia: Japan Clinical Oncology Group; Australia: TransTasman Radiation Oncology Group. Conflict of interest: none. AcknowledgmentsdThe authors would like to thank other active participants in the formation of the Global Clinical Trials RTQA Harmonization Group not listed as authors above: Australia: Tomas Kron, Martin Ebert, and Joan Hatton; Belgium: Akos Gulyban; Canada: Coreen Corning; Switzerland: Stefano Gianolini; United States: Jeff Michalski, Geoff Ibbott, Vikram Bhadrasain, Andrea Molineau, William Straube, and Ying Xiao.
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Harmonization of RTQA naming conventions 1243
Surrey County Hospital, Guildford, Surrey and National Physical Laboratory, Teddington, Middlesex, representing Radiation Therapy Trials Quality Assurance (RTTQA), United Kingdom; jjjjMount Vernon Cancer Centre, Northwood, Middlesex representing RTTQA, United Kingdom; {{Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland, Representing the EORTC-ROG, RTQA, Brussels, Belgium; ##Catharina Hospital, Eindhoven, The Netherlands, Representing EORTC-ROG, RTQA, Brussels, Belgium; and ***Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium Received Jun 17, 2014, and in revised form Aug 5, 2014. Accepted for publication Aug 28, 2014.
Summary Various radiation therapy quality assurance (RTQA) procedures and naming conventions are used by clinical trial groups worldwide. The Global Harmonisation Group here presents an overview of these procedures and names and a new harmonized RTQA naming convention for use in clinical trials incorporating RT. This overview, incorporating the harmonization of RTQA naming conventions from 27 to 10, will facilitate intergroup trial collaboration and simplify exchange and interpretation of RTQA results.
Purpose: To review the various radiation therapy quality assurance (RTQA) procedures used by the Global Clinical Trials RTQA Harmonization Group (GHG) steering committee members and present the harmonized RTQA naming conventions by amalgamating procedures with similar objectives. Methods and Materials: A survey of the GHG steering committee members’ RTQA procedures, their goals, and naming conventions was conducted. The RTQA procedures were classified as baseline, preaccrual, and prospective/retrospective data capture and analysis. After all the procedures were accumulated and described, extensive discussions took place to come to harmonized RTQA procedures and names. Results: The RTQA procedures implemented within a trial by the GHG steering committee members vary in quantity, timing, name, and compliance criteria. The procedures of each member are based on perceived chances of noncompliance, so that the quality of radiation therapy planning and treatment does not negatively influence the trial measured outcomes. A comparison of these procedures demonstrated similarities among the goals of the various methods, but the naming given to each differed. After thorough discussions, the GHG steering committee members amalgamated the 27 RTQA procedures to 10 harmonized ones with corresponding names: facility questionnaire, beam output audit, benchmark case, dummy run, complex treatment dosimetry check, virtual phantom, individual case review, review of patients’ treatment records, and protocol compliance and dosimetry site visit. Conclusions: Harmonized RTQA harmonized naming conventions, which can be used in all future clinical trials involving radiation therapy, have been established. Harmonized procedures will facilitate future intergroup trial collaboration and help to ensure comparable RTQA between international trials, which enables meta-analyses and reduces RTQA workload for intergroup studies. Ó 2014 Elsevier Inc.
Introduction The Global Clinical Trials Quality Assurance of Radiation Therapy Harmonization Group (GHG) (1) includes representation from clinical trial quality assurance (QA) offices from around the world (www.RTQAHarmonisation.org). The GHG’s main objective is to harmonize and improve the radiation therapy (RT) QA within multi-institutional cooperative clinical trials for the treatment of cancer (2). The steering committee members at present are detailed in the first-page footnote. All organizations and cooperative groups participating in the GHG ensure the quality of RT through their own established QA procedures, with some originating more than 40 years ago (3). Further information on the GHG can be found at the group’s website. There are some distinct variations within and between each group’s RTQA procedures found in the literature
(4-6), and this often complicates intergroup trial cooperation. For some intergroup trials, the RTQA is performed through adaption to one of the participating groups’ RTQA procedures, whereas in other trials each group follows its own procedures. For example, within the EORTC 10853Ductal Carcinoma In-Situ (DCIS) intergroup trial (7), the RTQA is centrally performed by EORTC-ROG using their RTQA infrastructure. Similarly, the patient-specific RTQA of the new joint Radiation Therapy Oncology Group (RTOG) 0848-EORTC 40084 trial is performed through infrastructure made available by RTOG. On the other hand, the RTQA within the Supremo trial (8) is performed by several RTQA groups (RTTQA, EORTC, and TransTasman Radiation Oncology Group [TROG]). Although these examples show that intergroup trial cooperation is already possible, the absence of harmonized procedures made the initiation of RTQA within these trials more labor intensive and complicated than needed. Additionally,
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coordination of RTQA activities, as well as RTQA data analysis and interpretation, is hampered by the lack of harmonized procedures. Additionally, for sites recruiting to a variety of clinical trial groups, the investigator site often needs to perform similar tasks for each separate trial group. Furthermore, meta-analyses of RTQA clinical trial data are now hindered by the large variety in RTQA procedures, which renders any meaningful intercomparison difficult. The purpose of this study was to review the various definitions and naming conventions of the RTQA procedures as defined in the RT section (or separate RT Planning and Delivery Guideline document) of each trial protocol used by each steering committee member’s organization within RT clinical trials. Given the observed similarities concerning the goals of the various globally implemented RTQA procedures within the GHG, a new harmonized set of RTQA procedures and corresponding naming conventions is presented.
accrue patients: export and upload a complete RT dataset into the GHG member’s reviewing software, adhere to the structure delineation and RT planning requirements of the protocol, or plan and deliver a specified dose using an advanced RT technique.
Methods and Materials A survey of the RTQA procedures of each GHG steering committee member was conducted. The results are presented in Table 1 and the definitions follow below.
Baseline For a site to participate in a clinical trial with RT, it must first become a participant within the QA program of a GHG member. Baseline QA procedures ensure that sites can meet minimum established requirements for trial participation as required by the GHG member.
Facility and basic dosimetric requirements Facility questionnaire The facility questionnaire collects information about the site’s contact personnel, workload, and RT and QA equipment and procedures. It ensures that minimum requirements established by the requesting GHG member (eg the maximum number of patients per specialist per year, available QA equipment) are met (9). Beam output audit/external reference dosimetry audit/ reference beam output This procedure is a verification of the dose delivery under reference conditions at the site. It is a dose measurement performed by a national or international auditor, independent from the site, and must meet specific requirements established by the requesting GHG member (10, 11). Variations exist among the GHG steering committee members concerning the measurement detector, geometry, frequency, number of beams, and RT machines to be evaluated.
Preaccrual Trial-specific preaccrual procedures verify that sites can meet any combination of the following before they begin to
Protocol-compliant dummy patient or site connectivity check Completing a test case is a common RTQA procedure. Quantifying the degree of variation from the protocol can determine the level of “education” or intervention required before trial accrual begins. A major deviation is a “significant” variation from the protocol that may affect the validity of interpretation of trial results, would this test case be an actual trial patient, whereas minor deviations may require education to prevent major deviations in actual trial patients (12). As an example, the nondelineation or not-accurate delineation of an organ at risk (OAR) may be considered a minor deviation, whereas the same observation on the margins between clinical and planned target volume may be considered a major deviation. Benchmark case by Radiological Physics Center (RPC) and TROG/dry run by Image-guided Therapy QA Center (ATC-ITC)/dummy run by EORTC-ROG, Japan Clinical Oncology Group (JCOG), and RTOG/outlining and planning cases/exercises by Radiation Therapy Trials Quality Assurance (RTTQA) Sites are required to contour and/or plan on a common set of CT datasets (which provides an opportunity to quantify contouring and planning variations between sites) according to the protocol and then successfully transmit the plan electronically to the GHG member. The procedure is sometimes split into 2 steps: a delineation exercise on a common set of CT datasets, and then a planning exercise on precontoured CT datasets (13, 14). Any variation is given as feedback to the site (with potential resubmission), so that protocol compliance will be improved during patient accrual. These procedures also test the clarity and feasibility of the RT instructions within the RT and RTQA section of a protocol and the RTQA guidelines before patient accrual begins and may lead to their further refinement. Benchmark case by EORTC-ROG and International Atomic Energy Agency (IAEA)/rapid review by RPC, RTOG, and ATC-ITC/pretrial case review by RTTQA/dummy run by TROG Sites are required to submit a protocol-compliant treatment plan on an in-house, nontrial patient with similar trial pathology. The dataset is checked for its integrity, delineation, and dose constraint compliance, and any variation is given as feedback to the site (with potential resubmission), to improve protocol agreement during patient accrual.
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RTQA procedures among the GHG steering committee members Baseline
Member ATC-ITC
Facility and basic dosimetric requirements Not performed
Prospective/retrospective RTQA data capture and analysis
Preaccrual Protocol-compliant dummy patient or site connectivity check Data submission test or rapid review or dry run
Advanced RT technique credentialing Not performed
Remote review of patients’ RT treatments
Site visits
Not performed 1. Basic archiving 2. 1 þ completeness check 3. 2 þ compute DVHs 4. 3 þ reconcile structures 5. 4 þ image registration and case report forms
EORTC-ROG Facility questionnaire and external reference dosimetry audit by RPC or other QA office IAEA Facility questionnaire and reference beam output JCOG Facility questionnaire and external reference dosimetry audit RPC Facility questionnaire and OSLD/TLD beam output audit
Dummy run or Complex dosimetry digital data integrity check or virtual quality assurance phantom procedure
Individual case review Not and case report forms performed
Benchmark cases
Individual case review Not and case report forms performed Individual case review Not and case report forms performed
RTOG
Facility questionnaire and external reference dosimetry audit by RPC
Dummy run or rapid review or dry run
RTTQA
Facility questionnaire and external reference dosimetry audit by RTTQA or IPEM/NPL*
TROG
Facility questionnaire and external reference dosimetry audit (eg, ARPANSA/ACDS)
Outlining and planning cases/exercises or pretrial case review Benchmark cases or dummy run or digital data integrity quality assurance
Dummy run or digital data integrity quality assurance Benchmark cases or rapid review
Complex dosimetry check Complex dosimetry check
Credentialing for Review of patients’ advanced technology treatment records, clinical trials or timely reviews, complex dosimetry and case report check forms Credentialing for Individual case review advanced and case report technology forms clinical trials Credentialing for advanced techniques
Individual case review and case report forms/plan assessment form
Credentialing for advanced technology clinical trials
Individual case review and case report forms
On-site dosimetry review visits On-site dosimetry review visits by RPC On-site dosimetry visit
On-site dosimetry review visits by TROG (or approved service)
Abbreviations: ATC Z Advanced Technology Consortium; ARPANSA/ACDS Z Australian Radiation Protection and Nuclear Safety Agency/ Australian Clinical Dosimetry Service; EORTC-ROG Z European Organization for the Research and Treatment of CancereRadiation Oncology Group; GHG Z Global Clinical Trials RTQA Harmonization Group; IAEA Z International Atomic Energy Agency; IPEM/NPL Z Institute of Physics and Engineering in Medicine/National Physical Laboratory; ITCZ Image-guided Therapy QA Center; JCOG Z Japan Clinical Oncology Group; OSLD/ TLD Z optically stimulated/thermoluminescent dosimeter; RPC Z Radiological Physics Center; RTOG Z Radiation Therapy Oncology Group; RTQA Z Radiation Therapy Quality Assurance; RTTQA Z Radiation Therapy Trials Quality Assurance; TROG Z TransTasman Radiation Oncology Group.
Data submission test by ATC-ITC/dry run by RTOG/ digital data integrity quality assurance by EORTC-ROG, JCOG, and TROG A site is required to upload an in-house patient’s RT dataset that was planned using the same treatment technique and equipment to be used for patients within the
trial, including complete datasets from any imaging modalities and/or cone-beam CT. The dataset is checked for its integrity and anonymity of patient details, verifying that a site can export and upload the required datasets, so that prospective reviews meet protocol time frames.
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Advanced RT technique credentialing
reviewing a combination of diagnostic images and RT target volume and OAR structure sets and treatment plans or conducting site visits. Here again a major deviation is the same as under “Protocol-compliant dummy patient” (12).
The purpose of this credentialing is to increase the likelihood that sites have the “necessary expertise and resources” to safely implement new irradiation techniques, such as intensity modulated RT, volumetric modulated arc therapy, and Tomotherapy, in the context of a clinical trial (15). Currently there exist variations among the GHG members concerning the appropriate detectors, acceptable dose limits, frequency, and auditing bodies (3, 16). Complex dosimetry check (CDC) This end-to-end test uses a mailed phantom for planning CT acquisition, treatment planning, and dose delivery verification. The absolute doses between calculation and measurement must agree within predefined limits as set by the GHG member, and the dose is measured in at least 1 plane. The dosimeters are provided by the auditing organization and may include, for example, ion chambers, films, thermoluminescent dosimeters (TLDs), and optically stimulated luminescence dosimeters (OSLDs)/TLDs. Credentialing for advanced techniques by RTTQA and TROG This credentialing includes questionnaires and a process document (description and examples of all relevant procedures in recruiting site), verification of electronic transfer of data, outlining exercises, planning exercises, and dose point and distribution measurements on phantoms for both standard and clinical trial plans (16-20). This procedure is accomplished during site visits. Credentialing for advanced technology clinical trials by RPC and RTOG This procedure is accomplished either via a benchmark treatment plan or simulation, planning, and irradiation of an anthropomorphic phantom and includes the components of CDC, with the addition of questionnaires, a dosimetry review, and a review of the site’s QA, dosimetry procedures and records. Virtual phantom Sites use a provided CT dataset to plan a treatment according to specific guidelines. The plan is recalculated on the sites’ own QA phantom geometry, and the phantom is irradiated according to plan, avoiding the necessity of a phantom to be mailed to the site. The dataset and the required measurement files are uploaded to the EORTC for evaluation (21).
Prospective/retrospective RTQA data capture and analysis These procedures assure that the protocol requirements are being or have been followed for on-trial patients by
Remote review of patients’ RT treatments Timely review by RPC/individual case review by EORTCROG, IAEA, JCOG, RTOG, RTTQA, and TROG/image registration by ITC Timely review consists of review of the actual delineation and treatment plan of trial patients, including diagnostic images if applicable, to assess target volumes and OARs or repositioning. Where image-guided RT is used, organ motion and treatment response images may also be collected. This procedure assures protocol compliance of trial patients and can be done prospectively (22) or retrospectively (5, 23-25). Prospective review provides an opportunity for protocol compliance feedback to the site, such that delineation and planning changes can be made before the patient begins treatment. Prospective feedback reduces protocol deviations, creating stronger statistical significance for the results of the trial (22). Retrospective reviews that are fed back to the site during trial accrual may also have a positive impact on protocol compliance, but only for subsequent patients. When referring to the image registration procedure by ITC, it presupposes the previous use of “Basic Archiving,” “Completeness Check,” “Compute DoseeVolume Histograms,” and “Reconcile Structures.” Table 1 presents these last 4 procedures under ITC only: (1) Basic Archiving: Storing of patients’ RT datasets for possible future evaluation; (2) Completeness Check: Identical to data submission test but using trial patient datasets instead of “dummy patients”; (3) Compute DoseeVolume Histograms: A doseonly constraints protocol compliance check; (4) Reconcile Structures: A target volume and OAR delineation and dose constraints protocol compliance check. Review of patient’s treatment record by RPC Treatment plans are reviewed retrospectively to ensure that they have met the dosimetric and delineation requirements of the protocol. Measurements made at the site through the OSLD/TLD Beam Output Audit program and on-site dosimetry review visits (see below) are used, combined with the treatment parameters provided by the site (eg field size, depth, monitor unit [MU] setting), to independently verify the dose received by the patient. Case report forms/plan assessment form Sites retrospectively send paper or electronic reports concerning the RT treatment for all trial patients. The questions are predefined and usually include details of prescribed and delivered irradiations, as well as volume sizes and dose distribution to them. Although some of this information can be extracted from the review of the RT plan, this only represents what was planned for the patient. Efforts are already being
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conducted by the National Cancer Institute of the United States towards the global harmonization of case report forms (26).
Site visits On-site dosimetry visit by RTTQA This is a visit that ensures consistency between predicted and measured dose and includes measurements of output in reference conditions, as well as credentialing for advanced techniques using a protocol-compliant plan on a phantom. On-site dosimetry review visit by TROG A trial QA representative reviews the trial protocol with personnel from the site and observes the entire treatment process for a trial patient to confirm that the institution has properly implemented the protocol and to check for any protocol ambiguities. The procedure also includes measurements of output in reference conditions, as well as dose points and dose distributions using phantoms. On-site dosimetry review visit by RPC This consists of a review of the site’s treatment planning dosimetry data used to calculate beam-on time for each trial patient, the QA procedures and documentation, a review of treatment records to ascertain the consistency of the procedures used for treatment planning and MU calculations, and also includes dosimetry measurements.
Results The RTQA required within a clinical trial is based on the RT section of each trial protocol. Because RTQA’s mission is to ensure RT protocol compliance of all participating sites, the RT section must be comprehensive, be clear, and identify the RTQA required. A reason for the existence of differences in procedures among the GHG members may be the nonstandardization of the RT protocol section (27). The GHG steering committee members strive to reduce RT protocol noncompliance in delineation, planning, and treatment delivery through their individually established RTQA procedures. The procedures follow good clinical practice and international standards; however, they differ in quantity, timing, title, and compliance criteria. The baseline RTQA procedures between the RTQA groups are the same for each trial and participating site, whereas the preaccrual and prospective/retrospective data capture and analysis procedures vary per RTQA group and per trial (Table 1), depending among others on the influence that the RT component may have on the trial’s main question and the level of RT technique complexity that is allowed or in question. The main differences between the procedures implemented by the various RTQA groups are detailed below: Baseline: No real differences exist, besides the different minimum requirements established per the GHG steering committee members.
Harmonization of RTQA naming conventions 1247
Protocol-compliant dummy patient or site connectivity check: There are differences in the depth of procedures, depending on the complexity of the trial and the relevance of RT to the trial’s question. Some of the procedures only check the site’s connectivity abilities, whereas others also check the protocol compliance on a “dummy patient.” Advanced RT technique credentialing: Complex dosimetry check and credentialing for advanced techniques by RTTQA and TROG use a physical phantom and dosimeters, both provided by the auditing body. Credentialing for advanced technology clinical trials by RPC and RTOG can be accomplished using in-house equipment, whereas virtual phantom procedure by EORTC-ROG is always accomplished using in-house equipment. The RTTQA, TROG, RPC, and RTOG procedures have an augmented workload, with the parallel hope of strengthening the participants’ knowledge and ability to participate in the trial. Remote review of patients’ RT treatments: All but one of the procedures review the trial patients’ delineations and RT plan prospectively, during patient treatment, or retrospectively, whereas review of patient’s treatment record by RPC also acts as an independent MU calculation procedure but is only carried out retrospectively. Site visits: Whereas RTTQA’s procedure consists of measurements of output in reference conditions and credentialing for advanced techniques, TROG and RPC procedures also observe the entire treatment process, also performing phantom measurements using a protocolcompliant plan. In addition to that, RPC’s procedure consists of MU calculations for all trial patients. An in-depth reading of the definition of each procedure shows that more than half of the 27 procedures have common goals but are labelled differently, whereas 4 of them are prerequisites to others. Using this information the GHG steering committee members have harmonized the RTQA naming conventions, reducing their number from 27 to 10 (Table 2). The new RTQA procedures are as follows: Facility questionnaire: Demographics, workload, and QA equipment and procedures of the site. Beam output audit: Beam output measurement under reference conditions. Benchmark case: Planning and/or delineation test on a common CT dataset. Dummy run (with or without delineation exercise): Using imaging data of an in-house patient, this procedure is either a protocol compliance treatment plan test or a simple connectivity check. Complex treatment dosimetry check: Dosimetric test of advanced treatment techniques using a phantom provided by the GHG member or approved external dosimetry audit group. Virtual phantom: dosimetric test of advanced treatment techniques using in-house phantom.
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Naming conventions of RTQA procedures of the GHG steering committee members
Naming convention categories Baseline
Preaccrual
Prospective/retrospective RTQA data capture and analysis
Current name
New name
Facility questionnaire External reference dosimetry audit OSLD/TLD beam output audit Reference beam output Benchmark case by RPC and TROG Dry run by ITC Dummy run by EORTC-ROG, JCOG, and RTOG Outlining and planning cases/exercises by RTTQA Digital data integrity quality assurance Dry run by RTOG Data submission test Benchmark case by EORTC-ROG, IAEA Dummy run by TROG Pretrial case review Rapid review Credentialing for advanced technology clinical trials Complex dosimetry check Credentialing for advanced techniques Virtual phantom procedure Image registration by Advanced Technology Consortium (having completeness check, basic archiving, compute doseevolume histograms, and reconcile structures as prerequisites) Individual case review Timely review Review of patients’ treatment records Case report forms On-site dosimetry review visit by RPC On-site dosimetry review visit by TROG On-site dosimetry visit
Facility questionnaire Beam output audit
Benchmark case
Dummy run (without delineation exercise)
Dummy run (with delineation exercise)
Complex treatment dosimetry check
Virtual phantom (Prospective or retrospective) individual case review
Review of patients’ treatment records Case report forms Protocol compliance and dosimetry site visit
Abbreviations as in Table 1.
(Prospective or retrospective) individual case review: Review of the actual treatment plan and delineation of trial patients. Review of patients’ treatment records: Retrospective review of the actual treatment plan and delineation of trial patients, combined with measurements and protocol compliance and dosimetry site visits. Case report forms: Review of retrospectively submitted forms by each site on all trial patients concerning their RT treatment. Protocol compliance and dosimetry site visit: Beam output audit and complex treatment dosimetry check. It may also include observations of the entire treatment process for a trial patient, trial patients’ MU calculations, local QA procedures, and documentation and review of treatment records.
Discussion This article presented the various RTQA procedures used by the GHG steering committee members. Several
differences were found concerning similar procedures. As an example, the frequency and number of beams to be analyzed in the beam output audit varies greatly, with RPC and RTOG asking for every machine and energy on a yearly basis, and EORTC-ROG asking for the lowest and highest energy every other year. Furthermore, IAEA uses TLDs, RPC, RTOG, and EORTC-ROG use OSLD/TLDs, and in other groups ion chambers or alanine would be acceptable. In addition, the acceptable limits differ, with EORTC-ROG and IAEA requiring results within 5% and RPC and RTOG asking for 3%. Another example is the different reviewing software used among the GHG steering committee members, as well as the analysis methods, dosimeters, phantom designs, and acceptable limits used for the complex treatment dosimetry check. Such different compliance criteria can be seen, for example, when comparing the RPC procedure with the RTTQA one, with the procedure compliance criteria for g analysis ranging from 7%/4 mm to 3%/ 3 mm, respectively (3, 16). The GHG has identified all these differences and is working toward their harmonization, keeping in mind the need to apply different trialspecific criteria.
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As yet there is no consensus regarding which RTQA procedures should be used per trial. Whereas for some trials a limited QA program is performed, for others very extensive tests are conducted. It might be worthwhile to investigate what the optimal combination for both high trial compliance and cost-effectiveness of RTQA procedures could be for a given trial on the basis of the trial specifics, like the trial’s main question, the complexity of the RT given, and the design of the study (28). This requires further research into the effectiveness of the various procedures and their combination (29). Out of the analysis of the 27 procedures that were identified among the GHG steering committee members, a harmonized set of 10 procedures was formulated to be used in all future RT clinical trials.
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14.
15. 16. 17.
18.
19.
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