Imaging And Radiation Oncology Core Research Articles

Impact of grid size on uniform scanning and IMPT plans in XiO treatment planning system for brain cancer.

The main purposes of this study are to: 1) evaluate the accuracy of XiO treatment planning system (TPS) for different dose calculation grid size based on head phantom measurements in uniform scanning proton therapy (USPT); and 2) compare the dosimetric results for various dose calculation grid sizes based on real computed tomography (CT) dataset of pediatric brain cancer treatment plans generated by USPT and intensity‐modulated proton therapy (IMPT) techniques. For phantom study, we have utilized the anthropomorphic head proton phantom provided by Imaging and Radiation Oncology Core (IROC). The imaging, treatment planning, and beam delivery were carried out following the guidelines provided by the IROC. The USPT proton plan was generated in the XiO TPS, and dose calculations were performed for grid size ranged from 1 to 3 mm. The phantom containing thermoluminescent dosimeter (TLDs) and films was irradiated using uniform scanning proton beam. The irradiated TLDs were read by the IROC. The calculated doses from the XiO for different grid sizes were compared to the measured TLD doses provided by the IROC. Gamma evaluation was done by comparing calculated planar dose distribution of 3 mm grid size with measured planar dose distribution. Additionally, IMPT plan was generated based on the same CT dataset of the IROC phantom, and IMPT dose calculations were performed for grid size ranged from 1 to 3 mm. For comparative purpose, additional gamma analysis was done by comparing the planar dose distributions of standard grid size (3 mm) with that of other grid sizes (1, 1.5, 2, and 2.5 mm) for both the USPT and IMPT plans. For patient study, USPT plans of three pediatric brain cancer cases were selected. IMPT plans were generated for each of three pediatric cases. All patient treatment plans (USPT and IMPT) were generated in the XiO TPS for a total dose of 54 Gy (relative biological effectiveness [RBE]). Treatment plans (USPT and IMPT) of each case was recalculated for grid sizes of 1, 1.5, 2, and 2.5 mm; these dosimetric results were then compared with that of 3 mm grid size. Phantom study results: There was no distinct trend exhibiting the dependence of grid size on dose calculation accuracy when calculated point dose of different grid sizes were compared to the measured point (TLD) doses. On average, the calculated point dose was higher than the measured dose by 1.49% and 2.63% for the right and left TLDs, respectively. The gamma analysis showed very minimal differences among planar dose distributions of various grid sizes, with percentage of points meeting gamma index criteria 1% and 1 mm to be from 97.92% to 99.97%. The gamma evaluation using 2% and 2 mm criteria showed both the IMPT and USPT plans have 100% points meeting the criteria. Patient study results: In USPT, there was no very distinct relationship between the absolute difference in mean planning target volume (PTV) dose and grid size, whereas in IMPT, it was found that the decrease in grid size slightly increased the PTV maximum dose and decreased the PTV mean dose and PTV D50%. For the PTV doses, the average differences were up to 0.35 Gy (RBE) and 1.47 Gy (RBE) in the USPT and IMPT plans, respectively. Dependency on grid size was not very clear for the organs at risk (OARs), with average difference ranged from −0.61 Gy (RBE) to 0.53 Gy (RBE) in the USPT plans and from −0.83 Gy (RBE) to 1.39 Gy (RBE) in the IMPT plans. In conclusion, the difference in the calculated point dose between the smallest grid size (1 mm) and the largest grid size (3 mm) in phantom for USPT was typically less than 0.1%. Patient study results showed that the decrease in grid size slightly increased the PTV maximum dose in both the USPT and IMPT plans. However, no distinct trend was obtained between the absolute difference in dosimetric parameter and dose calculation grid size for the OARs. Grid size has a large effect on dose calculation efficiency, and use of 2 mm or less grid size can increase the dose calculation time significantly. It is recommended to use grid size either 2.5 or 3 mm for dose calculations of pediatric brain cancer plans generated by USPT and IMPT techniques in XiO TPS.PACS numbers: 87.55.D‐, 87.55.ne, 87.55.dk

Optimizing the MLC model parameters for IMRT in the RayStation treatment planning system.

Unlike other commercial treatment planning systems (TPS) which model the rounded leaf end differently (such as the MLC dosimetric leaf gap (DLG) or rounded leaf‐tip radius), the RayStation TPS (RaySearch Laboratories, Stockholm, Sweden) models transmission through the rounded leaf end of the MLC with a step function, in which the radiation transmission through the leaf end is the square root of the average MLC transmission factor. We report on the optimization of MLC model parameters for the RayStation planning system. This (TPS) models the rounded leaf end of the MLC with the following parameters: leaf‐tip offset, leaf‐tip width, average transmission factor, and tongue and groove. We optimized the MLC model parameters for IMRT in the RayStation v. 4.0 planning system and for a Varian C‐series linac with a 120‐leaf Millennium MLC, and validated the model using measured data. The leaf‐tip offset is the geometric offset due to the rounded leaf‐end design and resulting divergence of the light/radiation field. The offset value is a function of the leaf‐tip position, and tabulated data are available from the vendor. The leaf‐tip width was iteratively evaluated by comparing computed and measured transverse dose profiles of MLC defined fields at dmax in water. In‐water profile comparisons were also used to verify the MLC leaf position (leaf‐tip offset). The average transmission factor and leaf tongue‐and‐groove width were derived iteratively by maximizing the agreement between measurements and RayStation TPS calculations for five clinical IMRT QA plans. Plan verifications were performed by comparing MapCHECK2 measurements and Monte Carlo calculations. The MLC model was validated using five test IMRT cases from the AAPM Task Group 119 report. Absolute gamma analyses (3 mm/3% and 2 mm/2%) were applied. In addition, computed output factors for MLC‐defined small fields (2×2,3×3,4×4,6×6 cm2) of both 6 MV and 18 MV photons were compared to those independently measured by the Imaging and Radiation Oncology Core (IROC), Houston, TX. 6 MV and 18 MV models were both determined to have the same MLC parameters: leaf‐tip offset=0.3 cm,2.5% transmission, and leaf tongue‐and‐groove width=0.05 cm. IMRT QA analysis for five test cases in TG‐119 resulted in a 100% passing rate with 3 mm/3% gamma analysis for 6 MV, and >97.5% for 18 MV. The passing rate was >94.6% for 6 MV and >90.9% for 18 MV when the 2 mm/2% gamma analysis criteria was applied. These results compared favorably with those published in AAPM Task Group 119. The reported MLC model parameters serve as a reference for other users.PACS number(s): 87.55.D, 87.56.nk

TU-EF-304-06: A Comparison of CT Number to Relative Linear Stopping Power Conversion Curves Used by Proton Therapy Centers

Purpose: To compare the CT Number (CTN) to Relative Linear Stopping Power (RLSP) conversion curves used by 14 proton institutions in their dose calculations. Methods: The proton institution’s CTN to RLSP conversion curves were collected by the Imaging and Radiation Oncology Core (IROC) Houston QA Center during its on-site dosimetry review audits. The CTN values were converted to scaled CT Numbers. The scaling assigns a CTN of 0 to air and 1000 to water to allow intercomparison. The conversion curves were compared and the mean curve was calculated based on institutions’ predicted RLSP values for air (CTN 0), lung (CTN 250), fat (CTN 950), water (1000), liver (CTN 1050), and bone (CTN 2000) points. Results: One institution’s curve was found to have a unique curve shape between the scaled CTN of 1025 to 1225. This institution modified its curve based on the findings. Another institution had higher RLSP values than expected for both low and high CTNs. This institution recalibrated their two CT scanners and the new data placed their curve closer to the mean of all institutions. After corrections were made to several conversion curves, four institutions still fall outside 2 standard deviations at very low CTNs (100–200), and two institutions fall outside between CTN 850–900. The largest percent difference in RLSP values between institutions for the specific tissues reviewed was 22% for the lung point. Conclusion: The review and comparison of CTN to RLSP conversion curves allows IROC Houston to identify any outliers and make recommendations for improvement. Several institutions improved their clinical dose calculation accuracy as a Result of this review. There is still area for improvement, particularly in the lung area of the curve. The IROC Houston QA Center is supported by NCI grant CA180803.

Radiotherapy Quality Assurance Report From Children's Oncology Group AHOD0031

A phase 3 trial assessing response-based therapy in intermediate-risk Hodgkin lymphoma mandated real-time central review of involved field radiation therapy (IFRT) and imaging records by a centralized review center to maximize protocol compliance. We report the impact of centralized radiation therapy review on protocol compliance. Review of simulation films, port films, and dosimetry records was required before and after treatment. Records were reviewed by study-affiliated or review center-affiliated radiation oncologists. A deviation of 6% to 10% from protocol-specified dose was scored as "minor"; a deviation of >10% was "major." A volume deviation was scored as "minor" if margins were less than specified or "major" if fields transected disease-bearing areas. Interventional review and final compliance review scores were assigned to each radiation therapy case and compared. Of 1712 patients enrolled, 1173 underwent IFRT at 256 institutions in 7 countries. An interventional review was performed in 88% of patients and a final review in 98%. Overall, minor and major deviations were found in 12% and 6% of patients, respectively. Among the cases for which ≥1 pre-IFRT modification was requested by the Quality Assurance Review Center and subsequently made by the treating institution, 100% were made compliant on final review. By contrast, among the cases for which ≥1 modification was requested but not made by the treating institution, 10% were deemed compliant on final review. In a large trial with complex treatment pathways and heterogeneous radiation therapy fields, central review was performed in a large percentage of cases before IFRT and identified frequent potential deviations in a timely manner. When suggested modifications were performed by the institutions, deviations were almost eliminated.

Institutional Patient-specific IMRT QA Does Not Predict Unacceptable Plan Delivery

To determine whether in-house patient-specific intensity modulated radiation therapy quality assurance (IMRT QA) results predict Imaging and Radiation Oncology Core (IROC)-Houston phantom results. IROC Houston's IMRT head and neck phantoms have been irradiated by numerous institutions as part of clinical trial credentialing. We retrospectively compared these phantom results with those of in-house IMRT QA (following the institution's clinical process) for 855 irradiations performed between 2003 and 2013. The sensitivity and specificity of IMRT QA to detect unacceptable or acceptable plans were determined relative to the IROC Houston phantom results. Additional analyses evaluated specific IMRT QA dosimeters and analysis methods. IMRT QA universally showed poor sensitivity relative to the head and neck phantom, that is, poor ability to predict a failing IROC Houston phantom result. Depending on how the IMRT QA results were interpreted, overall sensitivity ranged from 2% to 18%. For different IMRT QA methods, sensitivity ranged from 3% to 54%. Although the observed sensitivity was particularly poor at clinical thresholds (eg 3% dose difference or 90% of pixels passing gamma), receiver operator characteristic analysis indicated that no threshold showed good sensitivity and specificity for the devices evaluated. IMRT QA is not a reasonable replacement for a credentialing phantom. Moreover, the particularly poor agreement between IMRT QA and the IROC Houston phantoms highlights surprising inconsistency in the QA process.

TU‐C‐9A‐01: IROC Organization and Clinical Trial Credentialing

As a response to recommendations from a report from the Institute of Medicine, NCI is reorganizing it clinical trial groups into a National Clinical Trial Network (NCTN) that consists of four adult groups (Alliance, ECOGACRIN, NRG, and SWOG) and one children’s group (COG). NRG will house CIRO, a center to promote innovative radiation therapy research and intergroup collaboration in radiation. The quality assurance groups that support clinical trials have also been restructured. ITC, OSU Imaging corelab, Philadelphia Imaging core‐lab, QARC, RPC, and RTOGQA have joined together to create the Imaging and Radiation Oncology Core (IROC) Group. IROC’s mission is to provide integrated radiation oncology and diagnostic imaging quality control programs in support of the NCI’s NCTN thereby assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide. This will be accomplished through five core services: site qualification, trial design support, credentialing, data management, case review. These changes are important for physicist participating in NCI clinical trials to understand. We will describe in detail the IROC’s activities and five core services so that as a user, the medical physicist can learn how to efficiently utilize this group. We will describe common pitfalls encountered in credentialing for current protocols and present methods to avoid them. These may include the which benchmarks are required for NSABP B‐51/RTOG 1304 and how to plan them as well as tips for phantom planning. We will explain how to submit patient and phantom cases in the TRIAD system used by IROC.Learning Objectives: To understand the basic organization of IROC, its mission and five core services To learn how to use TRIAD for patient and phantom data submission To learn how to avoid common pitfalls in credentialing for current trials

SU‐E‐P‐02: Imaging and Radiation Oncology Core (IROC) Houston QA Center (RPC) Credentialing

Purpose:To provide information pertaining to IROC Houston QA Center's (RPC) credentialing process for institutions participating in NCI‐sponsored clinical trials.Methods:IROC Houston issues credentials for NCI sponsored study groups. Requirements for credentialing might include any combination of questionnaires, knowledge assessment forms, benchmarks, or phantom irradiations. Credentialing requirements for specific protocols can be found on IROC Houston's website (irochouston.mdanderson.org). The website also houses the credentialing status inquiry (CSI) form. Once an institution has reviewed the protocol's credentialing requirements, a CSI form should be completed and submitted to IROC Houston. This form is used both to request whether requirements have been met as well as to notify IROC Houston that the institution requests credentialing for a specific protocol. IROC Houston will contact the institution to discuss any delinquent requirements. Once the institution has met all requirements IROC Houston issues a credentialing letter to the institution and will inform study groups and other IROC offices of the credentials. Institutions can all phone the IROC Houston office to initiate credentialing or ask any credentialing related questions.Results:Since 2010 IROC has received 1313 credentialing status inquiry forms. We received 317 in 2010, 266 in 2011, 324 in 2012, and 406 in 2013. On average we receive 35 phone calls per week with multiple types of credentialing questions. Decisions regarding credentialing status are based on the protocol specifications and previous completed credentialing by the institution. In some cases, such as for general IMRT credentialing, up to 5 sites may be credentialed based on the credentialing of one main center. Each of these situations is handled individually.Conclusion:IROC Houston will issue radiation therapy credentials for the NCI trials in the National Clinical Trials Network. Credentialing requirements and the CSI form can be found online at the IROC Houston's website.Work supported by PHS grant CA10953 and CA081647 (NCI, DHHS).

SU‐E‐CAMPUS‐T‐03: Development and Implementation of An Anthropomorphic Pediatric Spine Phantom for the Assessment of Craniospinal Irradiation Procedures in Proton Therapy

Purpose:To design an anthropomorphic pediatric spine phantom for use in the evaluation of proton therapy facilities for clinical trial participation by the Imaging and Radiation Oncology Core (IROC) Houston QA Center (formerly RPC).Methods:This phantom was designed to perform an end‐to‐end audit of the proton spine treatment process, including simulation, dose calculation by the treatment planning system (TPS), and proton treatment delivery. The design incorporated materials simulating the thoracic spinal column of a pediatric patient, along with two thermoluminescent dosimeter (TLD)‐100 capsules and radiochromic film embedded in the phantom for dose evaluation. Fourteen potential materials were tested to determine relative proton stopping power (RSP) and Hounsfield unit (HU) values. Each material was CT scanned at 120kVp, and the RSP was obtained from depth ionization scans using the Zebra multilayer ion chamber (MLIC) at two energies: 160 MeV and 250 MeV. To determine tissue equivalency, the measured RSP for each material was compared to the RSP calculated by the Eclipse TPS for a given HU.Results:The materials selected as bone, tissue, and cartilage substitutes were Techron HPV Bearing Grade (Boedeker Plastics, Inc.), solid water, and blue water, respectively. The RSP values did not differ by more than 1.8% between the two energies. The measured RSP for each selected material agreed with the RSP calculated by the Eclipse TPS within 1.2%.Conclusion:An anthropomorphic pediatric proton spine phantom was designed to evaluate proton therapy delivery. The inclusion of multiple tissue substitutes increases heterogeneity and the level of difficulty for institutions to successfully treat the phantom. The following attributes will be evaluated: absolute dose agreement, distal range, field width, junction match and right/left dose profile alignment. The phantom will be tested at several institutions using a 5% dose agreement criterion, and a 5%/3mm gamma analysis criterion for the film planes.Work supported by grants CA10953, CA059267, and CA81647 (NCI, DHHS).

Development and implementation of an anthropomorphic pediatric spine phantom for the assessment of craniospinal irradiation procedures in proton therapy

Purpose: To design an anthropomorphic pediatric spine phantom for use in the evaluation of proton therapy facilities for clinical trial participation by the Imaging and Radiation Oncology Core (IROC) Houston QA Center (formerly RPC). Methods : This phantom was designed to perform an end-to-end audit of the proton spine treatment process, including simulation, dose calculation by the treatment planning system (TPS), and proton treatment delivery. The design incorporated materials simulating the thoracic spinal column of a pediatric patient, along with two thermoluminescent dosimeter (TLD)-100 capsules and radiochromic film embedded in the phantom for dose evaluation. Fourteen potential materials were tested to determine relative proton stopping power (RSP) and Hounsfield unit (HU) values. Each material was CT scanned at 120 kVp, and the RSP was obtained from depth ionization scans using the Zebra multi-layer ion chamber (MLIC) at two energies: 160 MeV and 250 MeV. To determine tissue equivalency, the measured RSP for each material was compared to the RSP calculated by the Eclipse TPS for a given HU. Results: The materials selected as bone, tissue, and cartilage substitutes were Techron HPV Bearing Grade (Boedeker Plastics, Inc.), solid water, and blue water, respectively. The RSP values did not differ by more than 1.8% between the two energies. The measured RSP for each selected material agreed with the RSP calculated by the Eclipse TPS within 1.2%. Conclusion : An anthropomorphic pediatric proton spine phantom was designed to evaluate proton therapy delivery. The inclusion of multiple tissue substitutes increases heterogeneity and the level of difficulty for institutions to successfully treat the phantom. The following attributes will be evaluated: absolute dose agreement, distal range, field width, junction match and right/left dose profile alignment. The phantom will be tested at several institutions using a 5% dose agreement criterion, and a 5%/3mm gamma analysis criterion for the film planes. -------------------------------------- Cite this article as: Lewis DJ, Summers PA, Followill DS, Sahoo N, Mahajan A, Stingo FC, Kry SF. Development and implementation of an anthropomorphic pediatric spine phantom for the assessment of craniospinal irradiation procedures in proton therapy. Int J Cancer Ther Oncol 2014; 2(2):020227. DOI: 10.14319/ijcto.0202.27

Abstract P5-14-19: Radiation field design on the ACOSOG Z0011 trial

Abstract Purpose/Objective: The landmark ACOSOG Z0011 trial established that axillary lymph node dissection (ALND) is unnecessary in breast cancer patients with one or two positive sentinel lymph nodes (SLN) who undergo lumpectomy, radiation therapy (RT) and systemic therapy. At a median follow-up of 6.3 years there were no differences in overall survival or local-regional recurrences between patients receiving ALND or SLN biopsy alone. The protocol required whole breast RT using standard tangential fields, but the extent of RT coverage of the regional nodes in these patients has not previously been described. We sought to ascertain this information. Methods: The RT data on the ACOSOG Z0011 trial was collected from case report forms completed by enrolling providers 18 months after enrollment. The response options on the forms included breast, supraclavicular, & other. We reviewed these data and, in 2011-2013, we attempted to identify and contact all treating radiation oncology practices to request detailed radiation treatment records for central review. RT data was sent to the Quality Assurance Review Center (QARC) and reviewed by two independent radiation oncologists, blinded regarding the arm to which the patients were randomized. Results: Of the 891 patients enrolled on Z0011, 35 withdrew consent prior to surgery, leaving 856 who were analyzed in the primary report on trial outcomes.1 Among the 605 of these patients with a completed adjuvant radiation therapy form, 89% were noted to receive whole breast RT. Of these, 89 patients (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were received on 228 patients: 104/389 (26.7%) and 124/404 (30.7%) on the ALND and SLND arms, respectively. Of the 228 patients, 185 patients (81.1%) received tangent-only treatment. Among these 185 patients, there was sufficient data to evaluate tangent field height in 142 (76.8%). High tangent RT fields (with cranial tangent border within 2 cm of the humeral head) were used in 52.6% (40/76) patients randomized to the ALND arm and 50% (33/66) patients randomized to the SLND arm. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥3 fields: 22 in the ALND and 21 in the SLND arm. Those receiving directed nodal RT tended to have greater nodal involvement (p<0.001). Conclusions: Most patients treated on the Z0011 trial received tangential field RT alone, and some received no radiotherapy at all. Some patients received directed nodal irradiation via a third field. In a subgroup for whom detailed RT records were available, the highest rates of directed nodal irradiation were among those with multiple nodes involved. As survival rates and local-regional recurrences were similar in the study arms, no conclusions can be drawn from this analysis on whether this additional radiation treatment was necessary or beneficial. 1JAMA 2011; 305 (6): 569-575. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-19.

WE‐G‐141‐01: The Imaging and Radiation Oncology Core (IROC) Group: A Proposed New Clinical Trial Quality Assurance Organization

Purpose: The NCI is implementing the new National Clinical Trial Network (NCTN) Program in 2014 reducing the number of existing study groups from ten to five. The NCTN Program also requires a new combined Imaging and Radiation Oncology Core (IROC) service to provide a uniform QA program. Methods: The six existing clinical trial QA centers, Radiological Physics Center, Quality Assurance Review Center, RTOG QA Center, Image Guided Therapy Center, ACRIN Core Lab and the CALGB Imaging Core Lab have combined to form IROC. The interdependencies between diagnostic imaging and radiation therapy (RT) will be synergized in IROC eliminating duplication of services within the network and optimizing efficient and effective workflows. A major strength of this new organization will be the development of consistent standard operating procedures for all imaging and RT aspects of the NCTN as well as to facilitate a seamless flow of imaging and RT datasets across the network. Results: IROC, administered though the American College of Radiology will provide the scientific and technical expertise in both diagnostic imaging and RT to the entire NCTN Program capitalizing on existing infrastructure and expertise at QA centers currently providing services to the NCI Cooperative Groups. IROC's organizational structure will allow the delivery of a broad array of imaging and RT QA services including Site Qualification; Trial Design Support; Credentialing; Data Management and Case Review. IROC will work closely with the leadership of each Network Group and NCI to assure them that imaging and RT data used by the Groups for protocol analysis are accurate. Conclusion: The proposed IROC Group has hundreds of collective years of experience conducting clinical trial QA and fully understands the QA needs/dataflow requirements of clinical trials to maintain the highest quality clinical trial data that will not obscure the outcomes of clinical trials. This work was supported by PHS grants CA10953, CA21661, CA029511 and CA081647 awarded by NCI, DHHS.

Radiation Therapy Quality Assurance on AHOD0031: A Report From the Quality Assurance Review Center (QARC) and the Children's Oncology Group

AHOD0031, a phase III trial assessing response-based therapy in intermediate-risk Hodgkin lymphoma, mandated central review of all radiation therapy (RT) and imaging records by QARC to maximize compliance with treatment and response evaluation guidelines. We report the impact of systematic RT data review on protocol compliance.

Quality assurance review center: Role in multi-institutional breast cancer trials.

205 Background: Central review is an important trial management and validation tool. Multisite trials require data systems to accommodate diverse image acquisition and review. Breast cancer is challenging as its imaging objects are not always easily shared across departments. Quality Assurance Review Center (QARC) has a diverse portfolio of facile data acquisition and powerful informatics support that meets these needs. We report on the role of QARC in three of the current breast cancer trials from the American College of Surgeons Oncology Group. Methods: QARC data management system includes secure network infrastructure and a validated relational operating database (MAX). QARC has data acquisition/imaging re-distribution expertise for real time response reviews, response measuring tools and corresponding data archive for secondary reviews. MAX includes query ability; records link to digital information. QARC underwent systematic information systems validation process for 21 CFR Part 11. DICOM/non-DICOM files are stored in the QARC PACS. On-site/remote reviewers use MAX to retrieve, view, annotate and save images. Data extracted is securely sent to partner statistical centers. Results: In Z1031, a neoadjuvant endocrine therapy trial, all of the mammographic exams are archived at QARC. For Z1071, a sentinel lymph node trial, pre- and post-treatment ultrasound (US) images of 321 patients were remotely reviewed. For Z1072, the cryoablation US, pre and post-cryoablation MRI for 40 of 47 cases were remotely archived, retrieved and transferred to investigator workstation for post-processing and review. The other 7 patients did not have evaluable imaging studies. In all three trials, the costs of shipping hardcopies of exams and travel to QARC for central review functions were eliminated. Conclusions: QARC data management systems provide diverse informatics supports for multi-institutional trials, ranging from archives of images, provide remote access and download of data, and central review. The vibrant informatics supports meet the growing needs of clinical trials. Future directions include radiation field review for breast cancer trials and the incorporation of pathology microarray analysis as DICOM objects.

SU-GG-T-259: Validation of CERR for Use as a Digital Data Review Tool at the Quality Assurance Review Center

Purpose: To develop a validation process for a software application to be used for digital RT data review in industry sponsored trials. Method and Materials: FDA guidance documents were used to formulate a validation process, which was applied to a customized version of the software application CERR (Computational Environment for Radiotherapy Research, http://radium.wustl.edu/CERR). The validation approach classified CERR as a 3rd party software application. As such, sufficient testing was required to establish that the software met “user needs and intended uses.” User requirements were specified and divided into six broad categories: (1) import functionality (both RTOG and DICOM RT), (2) viewer functionality, (3) plan tools (renaming, summing, beam data display), (4) structure tools (contouring, expanding, combining structures), (5) DVH tools, (6) study tools (anonymization, import log display). Eight data sets were identified for testing the functionality. Three data sets were in RTOG format; five were DICOM RT. Planning systems represented included Eclipse, Pinnacle and XiO. Studies were chosen that contained features relevant to the tests to be performed. For some of the studies planning system output in electronic format was available for comparison with CERR. 72 tests were performed, covering each area of the required functionality. Each test was assigned criteria for acceptability. Results: The results of eight tests, all related to DVH tools, did not meet the specified criteria. Discrepancies were noted for structures with small volumes and for structures receiving very low doses. Two tests had discrepancies because one structure was partially outside the dose grid. Conclusion: A validation process compliant with FDA guidelines has been developed and implemented to validate a digital RT review application. The validation test procedures will be made available to other review centers using similar software applications. This work was supported by NIH/NCI U10 Grant CA29511.

Critical Impact of Radiotherapy Protocol Compliance and Quality in the Treatment of Advanced Head and Neck Cancer: Results From TROG 02.02

To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer. The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality. At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; > or = 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): -2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively. These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.

Results of a Multi-Institutional Benchmark Test for Cranial CT/MR Image Registration

Variability in computed tomography/magnetic resonance imaging (CT/MR) cranial image registration was assessed using a benchmark case developed by the Quality Assurance Review Center to credential institutions for participation in Children's Oncology Group Protocol ACNS0221 for treatment of pediatric low-grade glioma. Two DICOM image sets, an MR and a CT of the same patient, were provided to each institution. A small target in the posterior occipital lobe was readily visible on two slices of the MR scan and not visible on the CT scan. Each institution registered the two scans using whatever software system and method it ordinarily uses for such a case. The target volume was then contoured on the two MR slices, and the coordinates of the center of the corresponding target in the CT coordinate system were reported. The average of all submissions was used to determine the true center of the target. Results are reported from 51 submissions representing 45 institutions and 11 software systems. The average error in the position of the center of the target was 1.8 mm (1 standard deviation = 2.2 mm). The least variation in position was in the lateral direction. Manual registration gave significantly better results than did automatic registration (p = 0.02). When MR and CT scans of the head are registered with currently available software, there is inherent uncertainty of approximately 2 mm (1 standard deviation), which should be considered when defining planning target volumes and PRVs for organs at risk on registered image sets.

Use of CERR at the Quality Assurance Review Center to Assess Protocol Compliance of Radiation Therapy Treatment Plans Submitted in Digital Format

To adapt the open source CERR application for use as a review tool to assess protocol compliance of radiation therapy treatment plans submitted in digital format to the Quality Assurance Review Center (QARC).

Quality Assurance Issues in Conducting Multi-Institutional Advanced Technology Clinical Trials

The National Cancer Institute-sponsored Advanced Technology Quality Assurance (QA) Consortium, which consisted of the Image-Guided Therapy QA Center, Radiation Therapy Oncology Group, Radiological Physics Center, Quality Assurance Review Center, and Resource Center for Emerging Technologies, has pioneered the development of an infrastructure and QA method for advanced technology clinical trials that requires volumetric digital data submission of a protocol patient's treatment plan and verification data. In particular, the Image-Guided Therapy QA Center has nearly 15 years experience in facilitating QA review for Radiation Therapy Oncology Group advanced technology clinical trials. This QA process includes (1) a data integrity review for completeness of protocol required elements, the format of data, and possible data corruption, and recalculation of dose-volume histograms; (2) a review of compliance with target volume and organ-at-risk contours by study chairs; and (3) a review of dose prescription and dose heterogeneity compliance by the Radiation Therapy Oncology Group Headquarters Dosimetry Group or the Radiological Physics Center dosimetrists (for brachytherapy protocols). This report reviews the lessons learned and the QA challenges presented by the use of advanced treatment modalities in clinical trials requiring volumetric digital data submission.

Developing a Multi-Institutional PACS Archive and Designing Processes to Manage the Shift from a Film to a Digital-Based Archive

The Quality Assurance Review Center (QARC) works to improve the standards of care in treating cancer by improving the quality of clinical trials medicine. QARC operates as a data management and review center providing quality assurance services for multiple external groups including cooperative groups and pharmaceutical companies. As the medical world migrates from analog film to digital files, QARC has developed an innovative and unique digital imaging management system to accommodate this trend. As QARC acquires electronic data from institutions across six continents, the system is continually developed to accommodate Digital Imaging and Communications in Medicine (DICOM) imaging originating from a wide variety of Picture Archival and Communications System (PACS) manufacturers, thus creating one of the largest and most diverse multi-institutional imaging archives in the cancer research community.

SU‐FF‐T‐267: Implementation of ATC Method 1 for Clinical Trials Data Review at the Quality Assurance Review Center

Purpose: To develop the capability at the Quality Assurance Review Center (QARC) to receive and review digital radiation therapy treatment planning data (TPD) for clinical trial case review. Method and Materials: A system of software (“ATC Method 1”) developed at the Image‐guided Therapy QA Center (ITC) as part of the Advanced Technology QA Consortium (ATC) to receive, process, and review volumetric TPD for clinical trials was ported to a Linux workstation at QARC. The system includes an FTP server for receiving TPD (in DICOM or RTOG data exchange format) from protocol participants, utilities for importing TPD into a local file format, and the web‐based Remote Review Tool (RRT) for QA of ROIs, isodoses, DVHs, and dose statistics. (Proprietary software components were used by special arrangement with CMS, Inc.) Results: Software installation and maintenance were performed remotely at QARC by ITC personnel, with weekly teleconferences to coordinate the development effort. ITC software was adapted to better support the QARC QA process. RRT enhancements include selectable DVHs, distance measurement tool, and image grayscale presets. QARC software was adapted to support RRT invocation directly from the QARC database user interface. The system is in use for six COG, CALGB, ACOSOG, and ECOG protocols; 28 cases from 15 institutions have been received and reviewed (3/1/06). Conclusion: Widespread use of new treatment modalities such as IMRT, makes use of 3D datasets essential for complete evaluation of ROI delineation and assessment of agreement of dosimetric parameters with protocol requirements. This project demonstrates that ATC Method 1, successfully used in support of RTOG trials for many years at ITC, can be implemented at other QA centers. The effort required, however, was significant and tools must be tailored to each individual QA center's computer infrastructure/QA process. Supported by NIH U24 Grant CA81647 and NCI‐H Grant 5U10CA02951.