title: Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials.
abstract: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps.
  
  
  
  Active PBT clinical trials were identified from clinicaltrials.gov and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted.
  
  
  
  A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% of trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy.
  
  
  
  The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address: mmishra@umm.edu.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Mishra
authors.affiliation: Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Sameer
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Soren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Nancy
authors.initials: N
authors.lastname: Knight
authors.affiliation: Miami Cancer Institute at Baptist Health South Florida, Miami, Florida.
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: William F
authors.initials: WF
authors.lastname: Regine
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000532:radiotherapy; D016543:Central Nervous System Neoplasms / Q000453:epidemiology / Q000532:radiotherapy; D002648:Child; D016208:Databases, Factual / Q000706:statistics & numerical data; D004938:Esophageal Neoplasms / Q000532:radiotherapy; D055317:Evidence-Based Practice; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000532:radiotherapy; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D063193:Heavy Ion Radiotherapy; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy; D008297:Male; D009369:Neoplasms / Q000453:epidemiology / Q000532:radiotherapy*; D064887:Observational Studies as Topic / Q000592:standards / Q000706:statistics & numerical data*; D018579:Patient Selection; D017785:Photons / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D061766:Proton Therapy / Q000592:standards / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000592:standards / Q000706:statistics & numerical data*; D012109:Research Support as Topic / Q000706:statistics & numerical data; D018401:Sample Size