An Evaluation of Worldwide Proton Beam Therapy Clinical Trials

Reporter: Jacob E. Shabason, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 4, 2013

Presenting Author: Mark Mishra, MD
Presenter'sAffiliation: Department of Radiation Oncology, University of Maryland, Baltimore, MD


  • Proton radiotherapy deposits the majority of its dose at a given depth in tissue (known as the Bragg Peak) with essentially no exit dose. As such, compared to standard photon radiation, protons may be able to better spare surrounding normal tissue and decrease early and late radiation toxicity.
  • Although proton therapy has been utilized for the treatment of a variety of malignancies over the past few decades there is limited data comparing outcomes to standard photon therapy.
  • Given the expense of proton therapy there are increased pressures from providers, policy makers and payers to rigorously study the efficacy and safety of proton radiotherapy in order to develop evidence based guidelines to guide the most appropriate use of proton therapy.
  • As such, the authors sought to evaluate all the current prospective clinical trials involving proton therapy and identify any major gaps in study that are in need of further prospective evaluation.


  • Currently ongoing clinical trials involving proton radiotherapy were identified from a national registry of studies at
  • Information of trial design, patient population, accrual goals and endpoints were extracted from this website.


  • There are currently 97 active clinical trials involving proton radiotherapy with the goal of accruing 20,202 patients worldwide.
  • The most common study design was phase 2 trials (47%), followed by observational (21%), phase 1/2 (11%), phase 3 (9%), pilot (7%), phase 1 (2%) and phase 2/3 (3%) studies.
  • Only 6% of trials will randomize patients between proton and photon therapy and only 4% between proton and carbon ion therapy.
  • The most common disease site studied are tumors of the central nervous system (23%), followed by gastrointestinal (17%,), genitourinary (17%), thoracic (10%), multiple (10%), head/neck (8%), breast (7%), sarcoma (4%), lymphoma (3%), GYN (1%) and Benign (1%).
  • Pediatric patients were included in 16% of trials.

Author's Conclusions

  • Current proton therapy trials are predominantly registry or phase II singe institution trials.
  • There are a limited number of phase III trials comparing proton therapy to standard and more readily available photon therapy.
  • Future trial design should focus on comparative effectiveness of proton therapy compared to more conventional radiation techniques.

Clinical Implications

  • The authors present a very important review of current prospective clinical research involving proton therapy.
  • Although, proton therapy may often times be able to offer improved normal tissue sparing compared to conventional radiation therapy, the clinical implications of this dosimetric advantage has not been thoroughly studied in prospective trials.
  • Proton therapy also currently costs significantly more than standard photon radiation, and in the current healthcare financial environment it is incumbent on the radiation oncology community to prove the clinical advantages of proton therapy to justify the increase in cost.
  • The majority of the current trials being either single institution registry or phase II trials provide important information regarding proton therapy.
  • However, there is an important gap in proton therapy research in comparative effectiveness research.
  • Therefore, there is a significant need for more randomized phase III trials comparing proton therapy to more conventional photon radiation.


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