Abstract: Rotating shield brachytherapy (RSBT) is a novel form of high-dose-rate brachytherapy (HDR-BT) delivered through shielded, rotating, catheters, which provide unprecedented control over radiation dose distributions. RSBT is expected to provide superior sub-volume boosting and toxicity relative to any existing radiotherapy modality, resulting in a paradigm shift in HDR-BT for many cancer sites. Although RSBT was conceptualized more than ten years ago, its clinical implementation poses tremendous challenges, demanding fundamentally advanced innovative technologies. With recent development of radiation sources, an effective and efficient RSBT treatment planning system has become a limiting factor for clinical development of RSBT. To this end, this project will develop fundamentally novel technology and algorithms to break the formidable computational barriers to bring RSBT into clinic. We hypothesize that rotating shield brachytherapy, powered with advanced treatment planning techniques and software, will provide significant dosimetric improvements in tumor coverage and critical structure avoidance relative to conventional HDR-BT, with a clinically acceptable delivery time. We propose to: 1) Develop an efficient compressed sensing based RSBT inverse dose optimization method, enabling sparse intensity modulation and optimized homogeneity of dose distributions with smooth fluence maps in the resulting treatment plan. 2) Develop efficient shield sequencing methods to optimize the delivery of RSBT treatment plans, striving to achieve the best tradeoff between plan quality and treatment time, and to facilitate clinicians' decision making on selecting the best patient-specific treatment plan. 3) Dosimetrically validate the RSBT treatment planning system retrospectively with clinical cases of cervical cancers and prostate cancers previously treated with HDR-BT. As a result, our project will pave the road to make RSBT clinically available, triggering a new era in brachytherapy delivery.