feasibility of using proton therapy with acceptable side effects, even in patients who have had multiple prior courses of photon radiation. Comparison with other treatments A large study on comparative effectiveness of proton therapy was published by teams of the University of Pennsylvania and Washington University in St. Louis in JAMA Oncology, assessing if proton therapy in the setting of concurrent chemoradiotherapy is associated with fewer 90-day unplanned hospitalizations and overall survival compared with concurrent photon therapy and chemoradiotherapy. The study included 1483 adult patients with nonmetastatic, locally advanced cancer treated with concurrent chemoradiotherapy with curative intent and concluded, "proton chemoradiotherapy was associated with significantly reduced acute adverse events that caused unplanned hospitalizations, with similar disease-free and overall survival". A significant number of randomized controlled trials is currently recruiting, but only a limited number have been completed as of August 2020. A phase III randomized controlled trial of proton beam therapy versus radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma organized by the National Cancer Center in Korea showed better 2-year local progression-free survival for the proton arm and concluded that proton beam therapy (PBT) is "not inferior to RFA in terms of local progression-free survival and safety, denoting that either RFA or PBT can be applied to recurrent small HCC patients". A phase IIB randomized controlled trial of proton beam therapy versus IMRT for locally advanced esophageal cancer organized by University of Texas MD Anderson Cancer Center concluded that proton beam therapy reduced the risk and severity of adverse events compared with IMRT while maintaining similar progression free survival. Another Phase II Randomized Controlled Trial comparing photons versus protons for Glioblastoma concluded that patients at risk of severe lymphopenia could benefit from proton therapy. A team from Stanford University assessed the risk of secondary cancer after primary cancer treatment with external beam radiation using data from the National Cancer Database for 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system. The study included a total of 450,373 patients and concluded that proton therapy was associated with a lower risk of second cancer. The issue of when, whether, and how best to apply this technology is still under discussion by physicians and researchers. One recently introduced method, 'model-based selection', uses comparative treatment plans for IMRT and IMPT in combination with normal tissue complication probability (NTCP) models to identify patients who may benefit