The National Cancer Institute's Cancer Disparities Research Partnership Program: a unique funding model 20 years later.

The burden of cancer and access to effective treatment are not experienced equally by all in the United States. For underserved populations that often access the health-care system when their cancers are in advanced disease stages, radiation oncology services are essential. In 2001, the National Cancer Institute's (NCI's) Radiation Research Program created and implemented the Cancer Disparities Research Partnership Program (CDRP). CDRP was a pioneering funding model whose goal was to increase participation of medically underserved populations in NCI clinical trials. CDRP's Cooperative Agreement funding supported for awardees the planning, development, and conduct of radiation oncology clinical research in institutions not traditionally involved in NCI-sponsored research and cared for a disproportionate number of medically underserved, health-disparities populations. The awardee secured and provided support for mentorship from 1 of 2 NCI comprehensive cancer centers named in its application. Six CDRP awards were made over two 5-year funding periods ending in 2013, with the end-of-program accomplishments previously reported. With the current focus on addressing equity, diversity, and inclusion, the 6 principal investigators were surveyed, 5 of whom responded about the impact of CDRP on their institutions, communities, and personal career paths. The survey that was emailed included 10 questions on a 5-point Likert scale. It was not possible to collect patient data this long after completion of the program. This article provides a 20-year retrospective of the experiences and observations from those principal investigators that can inform those now planning, building, and implementing equity, diversity, and inclusion programs.

Biomarkers for Biodosimetry and Their Role in Predicting Radiation Injury.

Radiation-related normal tissue injury sustained during cancer radiotherapy or in a radiological or mass casualty nuclear incident is a major health concern. Reducing the risk and mitigating consequences of radiation injury could have a broad impact on cancer patients and citizens. Efforts to discover biomarkers that can determine radiation dose, predict tissue damage, and aid medical triage are underway. Exposure to ionizing radiation causes changes in gene, protein, and metabolite expression that needs to be understood to provide a holistic picture for treating acute and chronic radiation-induced toxicities. We present evidence that both RNA (mRNA, microRNA, long noncoding RNA) and metabolomic assays may provide useful biomarkers of radiation injury. RNA markers may provide information on early pathway alterations after radiation injury that can predict damage and implicate downstream targets for mitigation. In contrast, metabolomics is impacted by changes in epigenetics, genetics, and proteomics and can be considered a downstream marker that incorporates all these changes to provide an assessment of what is currently happening within an organ. We highlight research from the past 10 years to understand how biomarkers may be used to improve personalized medicine in cancer therapy and medical decision-making in mass casualty scenarios.

Moving Forward in the Next Decade: Radiation Oncology Sciences for Patient-Centered Cancer Care.

In a time of rapid advances in science and technology, the opportunities for radiation oncology are undergoing transformational change. The linkage between and understanding of the physical dose and induced biological perturbations are opening entirely new areas of application. The ability to define anatomic extent of disease and the elucidation of the biology of metastases has brought a key role for radiation oncology for treating metastatic disease. That radiation can stimulate and suppress subpopulations of the immune response makes radiation a key participant in cancer immunotherapy. Targeted radiopharmaceutical therapy delivers radiation systemically with radionuclides and carrier molecules selected for their physical, chemical, and biochemical properties. Radiation oncology usage of "big data" and machine learning and artificial intelligence adds the opportunity to markedly change the workflow for clinical practice while physically targeting and adapting radiation fields in real time. Future precision targeting requires multidimensional understanding of the imaging, underlying biology, and anatomical relationship among tissues for radiation as spatial and temporal "focused biology." Other means of energy delivery are available as are agents that can be activated by radiation with increasing ability to target treatments. With broad applicability of radiation in cancer treatment, radiation therapy is a necessity for effective cancer care, opening a career path for global health serving the medically underserved in geographically isolated populations as a substantial societal contribution addressing health disparities. Understanding risk and mitigation of radiation injury make it an important discipline for and beyond cancer care including energy policy, space exploration, national security, and global partnerships.

Achieving flexible competence: bridging the investment dichotomy between infectious diseases and cancer.

Today's global health challenges in underserved communities include the growing burden of cancer and other non-communicable diseases (NCDs); infectious diseases (IDs) with epidemic and pandemic potential such as COVID-19; and health effects from catastrophic 'all hazards' disasters including natural, industrial or terrorist incidents. Healthcare disparities in low-income and middle-income countries and in some rural areas in developed countries make it a challenge to mitigate these health, socioeconomic and political consequences on our globalised society. As with IDs, cancer requires rapid intervention and its effective medical management and prevention encompasses the other major NCDs. Furthermore, the technology and clinical capability for cancer care enables management of NCDs and IDs. Global health initiatives that call for action to address IDs and cancer often focus on each problem separately, or consider cancer care only a downstream investment to primary care, missing opportunities to leverage investments that could support broader capacity-building. From our experience in health disparities, disaster preparedness, government policy and healthcare systems we have initiated an approach we call flex-competence which emphasises a systems approach from the outset of program building that integrates investment among IDs, cancer, NCDs and disaster preparedness to improve overall healthcare for the local community. This approach builds on trusted partnerships, multi-level strategies and a healthcare infrastructure providing surge capacities to more rapidly respond to and manage a wide range of changing public health threats.

Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials.

There is an urgent need to improve reproducibility and translatability of preclinical data to fully exploit opportunities for molecular therapeutics involving radiation and radiochemotherapy. For in vitro research, the clonogenic assay remains the current state-of-the-art of preclinical assays, whereas newer moderate and high-throughput assays offer the potential for rapid initial screening. Studies of radiation response modification by molecularly targeted agents can be improved using more physiologic 3D culture models. Elucidating effects on the cancer stem cells (CSC, and CSC-like) and developing biomarkers for defining targets and measuring responses are also important. In vivo studies are necessary to confirm in vitro findings, further define mechanism of action, and address immunomodulation and treatment-induced modification of the microenvironment. Newer in vivo models include genetically engineered and patient-derived xenograft mouse models and spontaneously occurring cancers in domesticated animals. Selection of appropriate endpoints is important for in vivo studies; for example, regrowth delay measures bulk tumor killing, whereas local tumor control assesses effects on CSCs. The reliability of individual assays requires standardization of procedures and cross-laboratory validation. Radiation modifiers must be tested as part of clinical standard of care, which includes radiochemotherapy for most tumors. Radiation models are compatible with but also differ from those used for drug screening. Furthermore, the mechanism of a drug as a chemotherapeutic agent may be different from its interaction with radiation and/or radiochemotherapy. This provides an opportunity to expand the use of molecular-targeted agents. Clin Cancer Res; 22(13); 3138-47. ©2016 AACR.

Combining targeted agents with modern radiotherapy in soft tissue sarcomas.

Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes.

Modifying normal tissue damage postirradiation. Report of a workshop sponsored by the Radiation Research Program, National Cancer Institute, Bethesda, Maryland, September 6-8, 2000.

Late effects that develop in normal tissues adjacent to the tumor site in the months to years after radiotherapy can reduce the quality of life of cancer survivors. They can be dose-limiting and debilitating or life-threatening. There is now evidence that some late effects may be preventable or partially reversible. A workshop, "Modifying Normal Tissue Damage Postirradiation", was sponsored by the Radiation Research Program of the National Cancer Institute to identify the current status of and research needs and opportunities in this area. Mechanistic, genetic and physiological studies of the development of late effects are needed and will provide a rational basis for development of treatments. Interdisciplinary teams will be needed to carry out this research, including pathologists, physiologists, geneticists, molecular biologists, experts in functional imaging, wound healing, burn injury, molecular biology, and medical oncology, in addition to radiation biologists, physicists and oncologists. The participants emphasized the need for developing and choosing appropriate models, and for radiation dose-response studies to determine whether interventions remain effective at the radiation doses used clinically. Both preclinical and clinical studies require long-term follow-up, and easier-to-use, more objective clinical scoring systems must be developed and standardized. New developments in biomedical imaging should provide useful tools in all these endeavors. The ultimate goals are to improve the quality of life and efficacy of treatment for cancer patients treated with radiotherapy.