Development and testing of a database of NIH research funding of AAPM members: A report from the AAPM Working Group for the Development of a Research Database (WGDRD).

PURPOSE: To produce and maintain a database of National Institutes of Health (NIH) funding of the American Association of Physicists in Medicine (AAPM) members, to perform a top-level analysis of these data, and to make these data (hereafter referred to as the AAPM research database) available for the use of the AAPM and its members. METHODS: NIH-funded research dating back to 1985 is available for public download through the NIH exporter website, and AAPM membership information dating back to 2002 was supplied by the AAPM. To link these two sources of data, a data mining algorithm was developed in Matlab. The false-positive rate was manually estimated based on a random sample of 100 records, and the false-negative rate was assessed by comparing against 99 member-supplied PI_ID numbers. The AAPM research database was queried to produce an analysis of trends and demographics in research funding dating from 2002 to 2015. RESULTS: A total of 566 PI_ID numbers were matched to AAPM members. False-positive and -negative rates were respectively 4% (95% CI: 1-10%, N = 100) and 10% (95% CI: 5-18%, N = 99). Based on analysis of the AAPM research database, in 2015 the NIH awarded $USD 110M to members of the AAPM. The four NIH institutes which historically awarded the most funding to AAPM members were the National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, National Heart Lung and Blood Institute, and National Institute of Neurological Disorders and Stroke. In 2015, over 85% of the total NIH research funding awarded to AAPM members was via these institutes, representing 1.1% of their combined budget. In the same year, 2.0% of AAPM members received NIH funding for a total of $116M, which is lower than the historic mean of $120M (in 2015 USD). CONCLUSIONS: A database of NIH-funded research awarded to AAPM members has been developed and tested using a data mining approach, and a top-level analysis of funding trends has been performed. Current funding of AAPM members is lower than the historic mean. The database will be maintained by members of the Working group for the development of a research database (WGDRD) on an annual basis, and is available to the AAPM, its committees, working groups, and members for download through the AAPM electronic content website. A wide range of questions regarding financial and demographic funding trends can be addressed by these data. This report has been approved for publication by the AAPM Science Council.

Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations.

BACKGROUND: Clinical testing of new therapeutic interventions requires comprehensive, high-quality preclinical data. Concerns regarding quality of preclinical data have been raised in recent reports. This report examines the data on the interaction of 10 drugs with radiation and provides recommendations for improving the quality, reproducibility, and utility of future studies. The drugs were AZD6244, bortezomib, 17-DMAG, erlotinib, gefitinib, lapatinib, oxaliplatin/Lipoxal, sunitinib (Pfizer, Corporate headquarters, New York, NY), thalidomide, and vorinostat. METHODS: In vitro and in vivo data were tabulated from 125 published papers, including methods, radiation and drug doses, schedules of administration, assays, measures of interaction, presentation and interpretation of data, dosimetry, and conclusions. RESULTS: In many instances, the studies contained inadequate or unclear information that would hamper efforts to replicate or intercompare the studies, and that weakened the evidence for designing and conducting clinical trials. The published reports on these drugs showed mixed results on enhancement of radiation response, except for sunitinib, which was ineffective. CONCLUSIONS: There is a need for improved experimental design, execution, and reporting of preclinical testing of agents that are candidates for clinical use in combination with radiation. A checklist is provided for authors and reviewers to ensure that preclinical studies of drug-radiation combinations meet standards of design, execution, and interpretation, and report necessary information to ensure high quality and reproducibility of studies. Improved design, execution, common measures of enhancement, and consistent interpretation of preclinical studies of drug-radiation interactions will provide rational guidance for prioritizing drugs for clinical radiotherapy trials and for the design of such trials.

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.

Education and Training Needs in the Radiation Sciences: Problems and Potential Solutions.

This article provides a summary of presentations focused on critical education and training issues in radiation oncology, radiobiology and medical physics from a workshop conducted as part of the 60th Annual Meeting of the Radiation Research Society held in Las Vegas, NV (September 21-24, 2014). Also included in this synopsis are pertinent comments and concerns raised by audience members, as well as recommendations for addressing ongoing and future challenges.

Technology for Innovation in Radiation Oncology.

Radiation therapy is an effective, personalized cancer treatment that has benefited from technological advances associated with the growing ability to identify and target tumors with accuracy and precision. Given that these advances have played a central role in the success of radiation therapy as a major component of comprehensive cancer care, the American Society for Radiation Oncology (ASTRO), the American Association of Physicists in Medicine (AAPM), and the National Cancer Institute (NCI) sponsored a workshop entitled "Technology for Innovation in Radiation Oncology," which took place at the National Institutes of Health (NIH) in Bethesda, Maryland, on June 13 and 14, 2013. The purpose of this workshop was to discuss emerging technology for the field and to recognize areas for greater research investment. Expert clinicians and scientists discussed innovative technology in radiation oncology, in particular as to how these technologies are being developed and translated to clinical practice in the face of current and future challenges and opportunities. Technologies encompassed topics in functional imaging, treatment devices, nanotechnology, and information technology. The technical, quality, and safety performance of these technologies were also considered. A major theme of the workshop was the growing importance of innovation in the domain of process automation and oncology informatics. The technologically advanced nature of radiation therapy treatments predisposes radiation oncology research teams to take on informatics research initiatives. In addition, the discussion on technology development was balanced with a parallel conversation regarding the need for evidence of efficacy and effectiveness. The linkage between the need for evidence and the efforts in informatics research was clearly identified as synergistic.

The Quantitative Imaging Network: NCI's Historical Perspective and Planned Goals.

The purpose of this editorial is to provide a brief history of National Institutes of Health National Cancer Institute (NCI) workshops as related to quantitative imaging within the oncology setting. The editorial will then focus on the recently supported NCI initiatives, including the Quantitative Imaging Network (QIN) initiative and its organizational structure, including planned research goals and deliverables. The publications in this issue of Translational Oncology come from many of the current members of this QIN research network.

The Importance of Dosimetry Standardization in Radiobiology.

Radiation dose is central to much of radiobiological research. Precision and accuracy of dose measurements and reporting of the measurement details should be sufficient to allow the work to be interpreted and repeated and to allow valid comparisons to be made, both in the same laboratory and by other laboratories. Despite this, a careful reading of published manuscripts suggests that measurement and reporting of radiation dosimetry and setup for radiobiology research is frequently inadequate, thus undermining the reliability and reproducibility of the findings. To address these problems and propose a course of action, the National Cancer Institute (NCI), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Standards and Technology (NIST) brought together representatives of the radiobiology and radiation physics communities in a workshop in September, 2011. The workshop participants arrived at a number of specific recommendations as enumerated in this paper and they expressed the desirability of creating dosimetry standard operating procedures (SOPs) for cell culture and for small and large animal experiments. It was also felt that these SOPs would be most useful if they are made widely available through mechanism(s) such as the web, where they can provide guidance to both radiobiologists and radiation physicists, be cited in publications, and be updated as the field and needs evolve. Other broad areas covered were the need for continuing education through tutorials at national conferences, and for journals to establish standards for reporting dosimetry. This workshop did not address issues of dosimetry for studies involving radiation focused at the sub-cellular level, internally-administered radionuclides, biodosimetry based on biological markers of radiation exposure, or dose reconstruction for epidemiological studies.

NCI support for particle therapy: past, present, future.

In light of the rising worldwide interest in particle therapy, and proton therapy specifically in the United States, the National Cancer Institute (NCI) is being asked more often about funding for such research and facilities. Many of the questions imply that NCI is naive to the exciting possibilities inherent in particle therapies, and thus they wish to encourage NCI to initiate and underwrite such programs. In fact, NCI has a long track record of support for the translation of hadrons from the physics laboratory to the therapy clinic by way of technology development and scientific investigations of physical and biological processes as well as clinical outcomes. Early work has included continuous funding since 1961 of proton treatments for more than 15,000 patients and facility construction at the Harvard/Massachusetts General Hospital (MGH) site; treatment of 227 patients with the pi-meson facility at Los Alamos between 1974 and 1981; funding of more than $69M for seven neutron therapy centers between 1971 and 1989; many funded projects in boron neutron capture radiation therapy through the present time; and numerous radiobiology projects over the past 50 y. NCI continues to play an active role in the incorporation of protons into randomized clinical trials through the Children's Oncology Group, Radiation Therapy Oncology Group, and the Program Project Grant (P01), which is co-directed by the MGH and MD Anderson Cancer Center. This has required funding development and implementation of guidelines that enable intercomparison of dosimetry and treatment between facilities. NCI has also funded recent efforts to develop new physical processes for the production of particles such as protons. With regard to the future, while it is true that there are no specific funding opportunity announcements directed to particle therapy research, it is also true that NCI remains open to reviewing any research that is compatible with an established mechanism. However, given the very substantial resources that these facilities currently require along with the highly competitive economic environment that now exists, it is clear that scientific review of such grant applications will look to leverage the scientific pursuits that are the NCI mandate with the reality of the clinical practices, just as is the case for photon radiation research. Such leveraging should be enhanced by the growing opportunities and need for international collaborations. On the other hand, these collaborations are complicated by the fact that these particle therapies are now fully reimbursable modalities, which makes it difficult to separate research (the NCI mission) from clinical practice development. This paper seeks to illuminate these new realities in order to encourage the pursuit and funding of the scientific underpinnings of physical methods, radiobiology, and clinical practice with particle therapy.

Redesigning radiotherapy quality assurance: opportunities to develop an efficient, evidence-based system to support clinical trials--report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance.

PURPOSE: In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. METHODS AND MATERIALS: Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such as proton beam therapy, and the international harmonization of clinical trial QA. RESULTS: Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. CONCLUSION: Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based.

Improving cancer outcomes through international collaboration in academic cancer treatment trials.

PURPOSE: The need for international collaboration in cancer clinical trials has grown stronger as we have made progress both in cancer treatment and screening. We sought to identify those efforts already underway which facilitate such collaboration, as well as barriers to greater collaboration. METHODS: We reviewed the collective experiences of many cooperative groups, governmental organizations, nongovernmental organizations, and academic investigators in their work to build international collaboration in cancer clinical trials across multiple disease sites. RESULTS: More than a decade of work has led to effective global harmonization for many of the elements critical to cancer clinical trials. Many barriers remain, but effective international collaboration in academic cancer treatment trials should become the norm, rather than the exception. CONCLUSION: Our ability to strengthen international collaborations will result in maximization of our resources and patients, permitting us to change practice by establishing more effective therapeutic strategies. Regulatory, logistical, and financial hurdles, however, often hamper the conduct of joint trials. We must work together as a global community to overcome these barriers so that we may continue to improve cancer treatment for patients around the world.

Current status and future potential of advanced technologies in radiation oncology. Part 1. Challenges and resources.

In 2006, the Radiation Research Program of the Division of Cancer Treatment and Diagnosis of the National Cancer Institute hosted a workshop intended to address current issues related to advanced radiation therapy technologies, with an eye toward (1) defining the specific toxicities that have limited the success of "conventional" radiation therapy, (2) examining the evidence from phase III studies for the improvements attributed to the advanced technologies in the treatment of several cancers commonly treated with radiation therapy, and (3) determining the opportunities and priorities for further technologic development and clinical trials. The new technologies offer substantial theoretical advantage in radiation dose distributions that, if realized in clinical practice, may help many cancer patients live longer and/or better. The precision of the advanced technologies may allow us to reduce the volume of normal tissue irradiated in the vicinity of the clinical target volume. Part 1 of this two-part article will provide a general overview of the workshop discussion, focusing on the challenges posed by the new technologies and resources available or in development for meeting those challenges. Part 2, which will appear in next month's issue of ONCOLOGY, will address the state of the science for each disease site.

Current status and future potential of advanced technologies in radiation oncology. Part 2. State of the science by anatomic site.

In December 2006, the Radiation Research Program of the Division of Cancer Treatment and Diagnosis of the National Cancer Institute hosted a workshop intended to address current issues related to advanced radiation therapy technologies, with an eye toward (1) defining the specific toxicities that have limited the success of "conventional" radiation therapy, (2) examining the evidence from phase III studies for the improvements attributed to the advanced technologies in the treatment of several cancers commonly treated with radiation therapy, and (3) determining the opportunities and priorities for further technologic development and clinical trials. The new technologies offer substantial theoretical advantage in radiation dose distributions that, if realized in clinical practice, may help many cancer patients live longer and/or better. The precision of the advanced technologies may allow us to reduce the volume of normal tissue irradiated in the vicinity of the clinical target volume. Part 1 of this two-part article, which appeared in the March issue of ONCOLOGY, provided a general overview of the workshop discussion, focusing on the challenges posed by the new technologies and resources available or in development for meeting those challenges. This month, part 2 will outline the state of the science for each disease site.

Quality assurance needs for modern image-based radiotherapy: recommendations from 2007 interorganizational symposium on "quality assurance of radiation therapy: challenges of advanced technology".

This report summarizes the consensus findings and recommendations emerging from 2007 Symposium, "Quality Assurance of Radiation Therapy: Challenges of Advanced Technology." The Symposium was held in Dallas February 20-22, 2007. The 3-day program, which was sponsored jointly by the American Society for Therapeutic Radiology and Oncology (ASTRO), American Association of Physicists in Medicine (AAPM), and National Cancer Institute (NCI), included >40 invited speakers from the radiation oncology and industrial engineering/human factor communities and attracted nearly 350 attendees, mostly medical physicists. A summary of the major findings follows. The current process of developing consensus recommendations for prescriptive quality assurance (QA) tests remains valid for many of the devices and software systems used in modern radiotherapy (RT), although for some technologies, QA guidance is incomplete or out of date. The current approach to QA does not seem feasible for image-based planning, image-guided therapies, or computer-controlled therapy. In these areas, additional scientific investigation and innovative approaches are needed to manage risk and mitigate errors, including a better balance between mitigating the risk of catastrophic error and maintaining treatment quality, complimenting the current device-centered QA perspective by a more process-centered approach, and broadening community participation in QA guidance formulation and implementation. Industrial engineers and human factor experts can make significant contributions toward advancing a broader, more process-oriented, risk-based formulation of RT QA. Healthcare administrators need to appropriately increase personnel and ancillary equipment resources, as well as capital resources, when new advanced technology RT modalities are implemented. The pace of formalizing clinical physics training must rapidly increase to provide an adequately trained physics workforce for advanced technology RT. The specific recommendations of the Symposium included the following. First, the AAPM, in cooperation with other advisory bodies, should undertake a systematic program to update conventional QA guidance using available risk-assessment methods. Second, the AAPM advanced technology RT Task Groups should better balance clinical process vs. device operation aspects--encouraging greater levels of multidisciplinary participation such as industrial engineering consultants and use-risk assessment and process-flow techniques. Third, ASTRO should form a multidisciplinary subcommittee, consisting of physician, physicist, vendor, and industrial engineering representatives, to better address modern RT quality management and QA needs. Finally, government and private entities committed to improved healthcare quality and safety should support research directed toward addressing QA problems in image-guided therapies.

Summary and recommendations of a National Cancer Institute workshop on issues limiting the clinical use of Monte Carlo dose calculation algorithms for megavoltage external beam radiation therapy.

Due to the significant interest in Monte Carlo dose calculations for external beam megavoltage radiation therapy from both the research and commercial communities, a workshop was held in October 2001 to assess the status of this computational method with regard to use for clinical treatment planning. The Radiation Research Program of the National Cancer Institute, in conjunction with the Nuclear Data and Analysis Group at the Oak Ridge National Laboratory, gathered a group of experts in clinical radiation therapy treatment planning and Monte Carlo dose calculations, and examined issues involved in clinical implementation of Monte Carlo dose calculation methods in clinical radiotherapy. The workshop examined the current status of Monte Carlo algorithms, the rationale for using Monte Carlo, algorithmic concerns, clinical issues, and verification methodologies. Based on these discussions, the workshop developed recommendations for future NCI-funded research and development efforts. This paper briefly summarizes the issues presented at the workshop and the recommendations developed by the group.