The present systematic review is an effort to explore the different clinical applications and current implementations of machine/deep learning in proton therapy. It will assist as a reference for scientists, researchers, and other health professionals who are working in the field of proton radiation therapy and need up-to-date knowledge regarding recent technological advances. This review utilized Pubmed and Embase to search for and identify research studies of interest published between 2019 and 2024. This systematic literature review utilized PubMed and Embase to search for and identify studies pertinent to machine learning in proton therapy. The time period of 2019 to 2024 was chosen to capture the most recent signficant advances. An initial search on PubMed was made with the search strategy ″′proton therapy′, ′machine learning′, ′deep learning′″, with filters including only research articles from 2019 to 2024, returning 84 results. Next, ″(″proton therapy″) AND (″machine learning″ OR ″deep learning″)″ was searched on Embase, retrieving 546 results. When filtered between 2019 to 2024 and to only research articles, 250 results were retrieved on Embase. Reviews, editorials, technical notes, and articles in any language other than English were excluded from the broad search on both databases. Filtering by title, papers were chosen based on two inclusion factors: explicit application to, or mention of, proton therapy, and inclusion of a machine learning algorithm. Assessing by abstract, works irrelevant to specific aspects of the proton therapy workflow in the scope of the review were excluded. Upon assessing and evaluating full texts for quality, studies were excluded that lacked a clear explanation of model architecture. If multiple studies of the same architecture applied to the same workflow step were identified, chronologically only the most recent advancement in application was included. An additional 5 studies that met all inclusion criteria were identified from references of chosen papers. In total, 38 relevant studies have been summarized and incorporated into this review. This is the first systematic review to comprehensively cover all current and potential areas of application of machine learning to the proton therapy clinical workflow.
