Maryann Bishop-Jodoin

Future vision for the quality assurance of oncology clinical trials

The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy, and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real-time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial.

Quality of radiotherapy reporting in randomized controlled trials of Hodgkin's lymphoma and non-Hodgkin's lymphoma: in regard to Bekelman and Yahalom (Int J Radiat Oncol Biol Phys 2009;73:492-498)

Drs. Bekelman and Yahalom’s (1) paper describing radiation therapy (RT) quality assurance (QA) in lymphoma clinical trials places emphasis for RT standards. Insuring study defined dose/volume constraint compliance, RTQA requires central pre-treatment diagnostic imaging and RT plan review. This letter describes Children’s Oncology Group (COG) historical and current RTQA process for Hodgkin’s lymphoma (HL) trials. For 33 years the Quality Assurance Review Center (QARC) has performed RTQA on cooperative group trials. Process improvements demonstrate maturing of clinical trials QA in response to protocol needs. The increasingly crucial role of imaging in clinical trials QA is validated. Pediatric Oncology Group (POG) protocol 8725 (intermediate/advanced staged HL) required 8 chemotherapy cycles +/− Involved Field RT. Initial publication(2) demonstrated no advantage for RT. Retrospective data review revealed 10% survival advantage for patients receiving compliant RT.(3) 30% of patients had treatment deviations including omission of RT to involved sites. To improve compliance, POG required pre-treatment RT review for next generation advanced/early stage HL studies, P9425/P9426(4,5). Strategy improved RT compliance. P9426 required post chemotherapy imaging response treatment adaptation. Retrospective response-imaging central review established that ~50% of patients had discordance between local and central review.(6) COG AHOD0031 (intermediate risk HL) included patient response-adapted therapy. QARC initiated real time response review with integrated imaging (anatomic and metabolic) and RT review prior to RT start. Discordant local and central interpretations were resolved in real time. (7,8) 1733 patients from 251 centers worldwide were enrolled. Near uniform data submission compliance has been obtained with >95% RT compliance in ~600 cases reviewed. Process feasibility allows extension of adaptive treatments based on centrally-confirmed response for the next high risk HL study. QARC-developed an informatics platform and processes that contribute to success of these clinical trials improvements. QARC acquires and manages imaging and RT data in several digital formats(9). The QARC database houses images and RT objects in side-by-side format, enabling remote investigator access. In collaborating with Dr. Purdy and the Advanced Technology Consortium, full digital RT files are received at QARC for review and DVH analysis. Currently strategies to incorporate Dicom compatible pathology objects into the database and use of open-source format for data sharing are being evaluated. The objectives identified in this paper for developing consensus standards and peer-review are in place for cooperative groups. Applying these established programs at enterprise level insures the objectives of this publication are met.

Imaging and Data Acquisition in Clinical Trials for Radiation Therapy

Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.

The Impact of Protocol Assignment for Older Adolescents with Hodgkin Lymphoma

Background and Purpose: Hodgkin lymphoma (HL) treatment has evolved to reduce or avoid radiotherapy (RT) dose and volume and minimize the potential for late effects. Some older adolescents are treated on adult protocols. The purpose of this study is to examine the protocol assignment of older adolescents and its impact on radiation dose to relevant thoracic structures. Materials and Methods: Cooperative group data were reviewed and 12 adolescents were randomly selected from a pediatric HL protocol. Treatment plans were generated per one pediatric and two adult protocols. Dose volume histograms for heart, lung, and breast allowed comparison of radiation dose to these sites across these three protocols. Results: A total of 15.2% of adolescents were treated on adult HL protocols and received significantly higher radiation dosage to heart and lung compared to pediatric HL protocols. Adolescents treated on either pediatric or adult protocols received similar RT dose to breast. Conclusion: Older adolescents treated on adult HL protocols received higher RT dose to thoracic structures except breast. Level of nodal involvement may impact overall RT dose to breast. The impact of varying field design and RT dose on survival, local, and late effects needs further study for this vulnerable age group. Adolescents, young adults, Hodgkin lymphoma, RT, clinical trials

Development of a Queriable Database for Oncology Outcome Analysis

Clinical trials and oncology data management have undergone considerable change in the past decade. Imaging has become a key tool for clinical trials management and a biomarker for clinical trial validation as imaging technologies improve and become more precise. Images have become extremely helpful in determining staging/eligibility, treatment response, and outcome determination including disease recurrence and progression. In modern protocols, images are often reviewed in real time to validate these points in order to improve compliance to study requirements and create uniform patient populations for clinical trials analysis. Data acquisition and management systems are currently in use to acquire and display images in electronic digital formats for view by both on site and off site radiology reviewers. As clinical trials become more global in focus, the ability for databases to accommodate diverse imaging acquisition strategies will become increasingly important for information review.

The Importance of Imaging in Radiation Oncology for National Clinical Trials Network Protocols

Imaging is essential in successfully executing radiation therapy (RT) in oncology clinical trials. As technically sophisticated diagnostic imaging and RT were incorporated into trials, quality assurance in the National Clinical Trials Network groups entered a new era promoting image acquisition and review. Most trials involving RT require pre- and post-therapy imaging for target validation and outcome assessment. The increasing real-time (before and during therapy) imaging and RT object reviews are to ensure compliance with trial objectives. Objects easily transmit digitally for review from anywhere in the world. Physician interpretation of imaging and image application to RT treatment plans is essential for optimal trial execution. Imaging and RT data sets are used to credential RT sites to confirm investigator and institutional ability to meet trial target volume delineation and delivery requirements. Real-time imaging and RT object reviews can be performed multiple times during a trial to assess response to therapy and application of RT objects. This process has matured into an effective data management mechanism. When necessary, site and study investigators review objects together through web media technologies to ensure the patient is enrolled on the appropriate trial and the intended RT is planned and executed in a trial-compliant manner. Real-time imaging review makes sure: (1) the patient is entered and eligible for the trial, (2) the patient meets trial-specific adaptive therapy requirements, if applicable, and (3) the intended RT is according to trial guidelines. This review ensures the study population is uniform and the results are believable and can be applied to clinical practice.

Hodgkin Lymphoma: Differences in Treatment Between Europe and the United States/North America: Evolving Trends in Protocol Therapy

With continued progress and success in clinical care, the management of patients with Hodgkin lymphoma (HL) has undergone continuous revision to improve patient care outcomes and limit acute and late treatment effects on normal tissue imposed by therapy. Hodgkin lymphoma is a disease that affects children, adolescents, and adults. Clinical management strategies are influenced by the patient’s age at diagnosis, tumor burden, response to induction therapy, and potential expectation of treatment impact on normal tissue. The approach to patient management varies in many parts of the world and is influenced by treatment availability, physician training, and medical culture. Differences in approach are important to understand for accurately comparing and contrasting outcome studies. In this article, we will identify current areas of common ground and points of separation in patient care management for HL. Opportunities for clinical trial strategies will be defined for future clinical trials.

Head and Neck Quality Assurance 2014

Quality assurance (QA) in complex head and neck cancer trials is essential. The need for QA is made more relevant with trials comprised of multiple end points, worldwide participation, and increasing use of adaptive strategies/advanced technology to validate/verify outcome analyses. Integration is necessary for tissue analysis, biomarker assessment, imaging, radiation therapy, chemotherapy, and/or targeted therapy for patients with new diagnosis, relapse, and second head and neck malignancies.

An Innovative Competency-based Oncology Course for First Year Medical Students

Future physicians will likely encounter patients with cancer or cancer survivors.Therefore the acquisition of core competencies in oncology is essential.1–3 We share our experience with the development and implementation of an oncology component in the recently redesigned Learner Centered Integrated Curriculum (LInC) at the University of Massachusetts Medical School. This pre-clinical course content is presented in a cross-disciplinary and longitudinal format that fosters problem solving, communication, lifelong learning skills, and professionalism throughout the undergraduate years and beyond.

Quality Assurance of Clinical Trials in the Management of Cancer in the Head and Neck

Integrating tissue analysis and imaging strategies in clinical trial objectives is an important area of clinical translational research. Clinical trial designs that incorporate clear guidelines for clinical trial execution, definitions of data submission pathways and study deviations, and integration of real time and adaptive quality assurance will provide uniformity of study populations for clinical trial analysis. Essential to clinical trials management is a robust, validated informatics platform to display data and imaging in a uniform manner acquired from diverse platforms and re-presented for both on site and distributed review in a uniform file format. The Quality Assurance Review Center (QARC) uses a robust informatics platform to provide protocol development, site credentialing, data acquisition, case management, capable of both real time and retrospective review of objects, data transfer to clinical trial sponsor and/or industry partner and data archiving. As a member of the Virtual Imaging Evaluation Workspace (VIEW) and the Advanced Technology Quality Assurance (QA) Consortium (ATC), QARC collaborates in the development, sharing and implementation of credentialing tools, digital acquisition and review tools and processes, a common platform for data storage for radiotherapy and imaging with emphasis on compliance to caBIG and 21 CFR Part 11. Recent evidence demonstrates that compliance to study guidelines may have significant influence on study and patient outcome. Head and neck cancer is a very good area to study biopharmacology of treatment response and the quality assurance process is a vehicle for adaptive clinical trial and patient management.