Summary Radiation therapy is an important tool in the cancer treatment arsenal. Conventional radiotherapy with photons is currently used to treat 50% of all cancer patients. The success of radiation therapy and the risk of side effects depend heavily on the ability to concentrate radiation in the tumor while not injuring adjacent normal tissues. Recent developments in radiation therapy instrumentation have increased the ability to direct radiation energy, thereby improving the clinical utility of this treatment. Although significant progress has been made, one of the limiting factors in the development of novel radiotherapy approaches is the size and cost of radiation sources. For many types of modern advanced radiotherapy, the equipment needed to produce such radiation is bulky and extremely expensive. At the same time, continuing advances in particle acceleration approaches enable breakthrough innovations in this field. An example of such advancement is the development of technologies for charged particle acceleration using high-power lasers (laser-plasma acceleration). New technologies enable the construction of compact, cost-efficient external beam accelerators, and facilitate new applications of radiotherapy. Another potential class of applications is the development of fiber-optics-based systems for endoscopic delivery of gamma or electron beams. These and other technologies present key opportunities in enabling next-generation radiation therapy instruments. Project Goals This contract topic seeks to stimulate research, development, and commercialization of innovative radiation sources that could be used to reduce the cost and footprint of radiation treatment systems, and thus enable novel routes for radiotherapy delivery. It is expected that the proposed innovation be driven by clinical practice. Therefore, in addition to standard proposal components, the contract proposal must contain specific discussion of: 1. Evidence of an existing clinical problem that is addressed by the proposed radiation source 2. Analysis of competitive methods to address the same problem and explanation of competitive advantages of proposed system. The short-term goal of the project is to perform proof-of-principle technical feasibility demonstration of innovative radiation source or source components. The long-term goal of the project is to develop a robust, reliable radiation source and to incorporate it into a radiotherapy system. Phase I Activities and Expected Deliverables Phase I activities should support the technical feasibility of the innovative approach. • Design and build proof-of-principle prototype system • Characterize beam parameters, including energy spectra, spatial distribution, and flux • Demonstrate that the prototype has a high probability of development into a clinically-relevant radiation source in Phase II, based on measured beam parameters • Provide documentation of the prototype system design, characterization protocol, and testing results to NCI as part of the Phase I progress report Phase II Activities and Expected Deliverables Phase II activities should support development of a full-scale prototype of a radiation source with beam parameters appropriate for the clinical application. • Design and develop a prototype radiation source with parameters (e.g., beam energy, flux, stability, etc.) that are acceptable for clinical radiation oncology application • Demonstrate that the system is capable of delivering a treatment dose in a clinically acceptable period of time in an anthropomorphic phantom • Provide a data sheet detailing performance of the developed system to NCI as part of the Phase II progress report Where cooperation with other equipment manufacturers is critical for implementation of proposed technology, company should provide evidence of such cooperation (through partnering arrangement, collaboration, or letters of intent) as part of the Phase II proposal.