James A. Deye

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.

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.

Electron Contamination of a High-energy X-ray Beam

The Lorentz force on an electron is utilised to separate out the electron component from the open beam of a Clinac-18, operating in the X-ray mode. The experimental arrangement is such that the mixed beam (comprising the primary photons, the scattered photons and the contamination electrons) enters an external magnetic field, which is perpendicular to the central axis of the beam. The electron contribution is analysed as a function of collimator setting, depth and distance. Based on the data, one is led to believe that the shift in dmax with field size is due to a relative enhancement in the soft X-ray component as the collimator jaws are opened.

Clinical observations of early and late normal tissue injury and tumor control in patients receiving fast neutron irradiation

Abstract The clinical experience of the first 211 patients treated at MANTA from October 1973 to May 1978 is described. Acute cutaneous, mucosal, gastrointestinal reactions and late effects including myelitis, damage to brain, bowel, soft tissue and mandibular necrosis are described. A review of tumor response data is also submitted.

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.

Effects of fractionated doses of fast neutrons and photons on the normal canine lung: relative biological effectiveness values obtained by radionuclide studies.

Abstract Thirty nine adult male beagles received either fast neutron or photon irradiation to the right thorax. There were 2 unirradiated control dogs. Twenty four dogs received fast neutrons with a mean energy of 15 MeV to total doses of 1000, 1500, 2250 or 3375 rad delivered in 4 fx/wk for 6 weeks. Fifteen dogs received total doses of 3000, 4500 or 6750 rad of photons ( 60 Co) in the same fractionation pattern. Radionuclide evaluations of pulmonary function were performed pre-irradiation and every three months post-irradiation for 1 year. These included: (1) radioaerosol deposition of an insoluble radiocolloid, 99m Tc-phytate; (2) 133 Xe ventilation studies; and (3) 99m Tc-macroaggregated albumin perfusion images. Values for the relative biological effectiveness (RBE) of fast neutrons in producing changes in these parameters have been obtained by plotting the changes from pre-irradiation values in the right lung as a function of the total dose. RBE values for the relative deposition of aerosol and the relative distribution of volume and perfusion have been obtained at 3, 6, 9 and 12 months post-irradiation. The relative biological effectiveness (RBE) for neutron damage to normal lung tissue was always greater than 4 in the clinical dose range of 4000–6000 rad of photons.

Overview of the American Society for Radiation Oncology–National Institutes of Health–American Association of Physicists in Medicine Workshop 2015: Exploring Opportunities for Radiation Oncology in the Era of Big Data

Big data research refers to the collection and analysis of large sets of data elements and interrelationships that are difficult to process with traditional methods. It can be considered a subspecialty of the medical informatics domain under data science and analytics. This approach has been used in many areas of medicine to address topics such as clinical care and quality assessment (1–3). The need for informatics research in radiation oncology emerged as an important initiative during the 2013 National Institutes of Health (NIH)–National Cancer Institute (NCI), American Society for Radiation Oncology (ASTRO), and American Association of Physicists in Medicine (AAPM) workshop on the topic “Technology for Innovation in Radiation Oncology” (4). Our existing clinical practice generates discrete, quantitative, and structured patient-specific data (eg, images, doses, and volumes) that position us well to exploit and participate in big data initiatives. The well-established electronic infrastructure within radiation oncology should facilitate the retrieval and aggregation of much of the needed data. With additional efforts to integrate structured data collection of patient outcomes and assessments into the clinical workflow, the field of radiation oncology has a tremendous opportunity to generate large, comprehensive patient-specific data sets (5). However, there are major challenges to realizing this goal. For example, existing data are presently housed across different platforms at multiple institutions and are often not stored in a standardized manner or with common terminologies to enable pooling of data. In addition, many important data elements are not routinely discretely captured in clinical practice. There are cultural, structural, and logistical challenges (eg, computer compatibility and workflow demands) that will make the dream of big data research difficult. The big data research workshop provided a forum for leaders in cancer registries, incident report quality-assurance systems, radiogenomics, ontology of oncology, and a wide range of ongoing big data and cloud computing development projects to interact with peers in radiation oncology to develop strategies to harness data for research, quality assessment, and clinical care. The workshop provided a platform to discuss items such as data capture, data infrastructure, and protection of patient confidentiality and to improve awareness of the wide-ranging opportunities in radiation oncology, as well as to enhance the potential for research and collaboration opportunities with NIH on big data initiatives. The goals of the workshop were as follows: To discuss current and future sources of big data for use in radiation oncology research, To identify ways to improve our current data collection methods by adopting new strategies used in fields outside of radiation oncology, and To consider what new knowledge and solutions big data research can provide for clinical decision support for personalized medicine.

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.

The effects of fractionated doses of fast neutrons or photons on the canine brain: Evaluation by computerized tomography and evoked response recording

Abstract The use of fast neutrons in the treatment of cancer necessitates a knowledge of the normal tissue responses. This study was designed to compare the late effects of fractionated doses of fast neutrons with fractionated doses of photons on canine brains by evoked response recording and viewing computerized tomograms (CT). Adult male beagles were irradiated to the entire brain (four fractions per week) with fast neutrons to total doses of 13.33 Gy (1333 rad), 20 Gy (2000 rad), 30 Gy (3000 rad) or 45 Gy (4500 rad) or with photons (four fractions per week) to total doses of 40 Gy (4000 rad), 60 Gy (6000 rad) or 90 Gy (9000 rad). A relative biological effectiveness (RBE) of 4 was obtained for normal brain tissue assessed by mortality and onset of neurologic symptoms. Every three months post-irradiation, visual and sensory evoked responses were recorded. Changes over time appeared to be minimal; however, computerized tomographs showed marked brain shrinkage. A method of quantitating cerebrospinal fluid and parenchyma) volumes from scans is described and future use of these CT ratios to generate dose response curves and RBE values is postulated.