Everyday Use of Optical Cherenkov Imaging Identifies Adverse Events and Opportunities for Improved Radiation Treatment - ABSTRACT Radiation therapy is a supplementary curative treatment used adjuvant with most surgery and chemotherapy, being delivered to nearly 1 out of every 4 people in their lifetime. External beam treatment is commonly fractionated (i.e. delivered every day for 25-40 days). While it is generally considered safe and effective, many in the field believe it could be safer. Major potential side effects can occur if not administered with high daily accuracy, including millimeter level patient alignment and care to keep normal tissue doses sufficiently low. However, there is a proven 1-5% incidence of secondary cancer from this treatment. This is particularly relevant in breast radiotherapy, where even a 1% dose to the contralateral breast has been proven to lead to a high probability for a secondary cancer. In reality, no clinic actually knows their true incident rate, because no system exists to visualize every treatment as part of routine clinical practice. The invention of the BeamSiteTM system, for time-gated single photon imaging of Cherenkov light emissions, provides the first direct video imaging of the radiation dose delivery as it happens. The system captures a direct visualization of delivery incidents in real time, so that intuitive observations can be made by the therapists and daily corrections can be made as needed. In this application, we will carry out a multicenter clinical study to investigate the capability of Cherenkov imaging to detect events which, heretofore, would go undetected. We will also advance the workflow of the system with automated incident detection tools to make BeamSiteTM easily used by the therapy team. Finally, the system will also be expanded with dose estimation algorithms to estimate long term secondary cancer risk. The project is based upon previous NIH supported hardware that is FDA 510(k) cleared for marketing and will be deployed with augmentation from the tools proposed here. The current proposal provides resources for the goals of: (i) quantifying error rates in the overall treatment of patients in multiple radiotherapy clinical settings, and (ii) quantify the unplanned dose delivered to non-target tissues, including contralateral breast in whole breast radiotherapy. The work includes software support and optical scintillator dosimetry development, to be leveraged towards these goals. The prospective human study of the incident rates will be carried out as a multisite effort within the Dartmouth-Hitchcock Health medical centers. The data produced with this system will demonstrate that visualization of treatment can change the way that daily radiotherapy is tracked and provide a tool for continuous improvement for each participating center, thereby reducing the secondary morbidity of off-target radiation. Financial reimbursement exists and as the field shifts to quality-based reimbursement versus quantity-based, Cherenkov imaging will become a staple of all leading radiotherapy units.