Charged-particle beams consisting of protons or helium ions are a type of particulate radiation therapy that contrast with conventional electromagnetic (i.e., photon) radiation therapy due to the unique properties of minimal scatter as the particulate beams pass through the tissue, and deposition of the ionizing energy at a precise depth (i.e., the Bragg Peak). Thus radiation exposure to surrounding normal tissues is minimized. The theoretical advantages of protons and other charged-particle beams may improve outcomes but this has not been proven. At the same time proton beam radiotherapy is significantly more expensive than other modalities.1
Australia and New Zealand Horizon Scanning Network (2006) stated that PBT “may be of particular benefit” in the treatment of patients with intermediate depth tumors such as those in the head, cancers that are located in difficult or dangerous-to-treat areas, and tumors in locations where “conventional radiotherapy would damage surrounding tissue to an unacceptable level” (e.g., central nervous system and head). PBT “may be ideal for use in the treatment of pediatric patients where the need to avoid secondary tumors is important due to the potentially long life span after radiation treatment when they may develop radiation induced malignancies.7
A report by ASTRO’s Emerging Technologies Committee states that there is reason to be optimistic about the potential developments in proton beam therapy (PBT) and the prospective research that is ongoing at centers worldwide. Current data do not provide sufficient evidence to recommend PBT outside of clinical trials in lung cancer, head and neck cancer, GI malignancies (with the exception of HCC) and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer, there is evidence of the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies, there is a suggestion from the literature that PBT is superior to photon approaches, but there is currently insufficient data to support a firm recommendation for PBT. In the setting of craniospinal irradiation for pediatric patients, protons appear to offer a dosimetric benefit over photons but more clinical data are needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. In all fields, however, further clinical research is needed and should be encouraged (ASTRO, 2011).
ACR appropriateness criteria state that the physical characteristics of the proton beam would seem to allow for greater sparing of normal tissues, although there are unique concerns about its use for lung tumors. The small amount of clinical data on its use consists of small single institution series. These data as a whole can be challenging to interpret, as various different techniques have been used by these institutions, making comparisons between studies difficult. Results from larger, prospective, controlled trials that are underway will clarify the role of proton beam and other particle therapies for lung cancer (ACR, 2010).4
A Blue Cross Blue Shield technology assessment evaluated health outcomes following proton beam therapy (PBT) compared to stereotactic body radiotherapy (SBRT) for the management of Proton Beam Radiation Therapy: Medical Policy 12 non-small-cell lung cancer. The report concluded that, overall, evidence is insufficient to permit conclusions about the results of PBT for any stage of non-small-cell lung cancer. All PBT studies are case series, and there are no studies directly comparing proton beam therapy (PBT) and stereotactic body radiotherapy (SBRT). In the absence of randomized, controlled trials, the comparative effectiveness of PBT and SBRT is uncertain (BCBS, 2011).6
The only guideline that I found that offers a qualified support is NCCN. The National Comprehensive Cancer Network (NCCN) states that the use of more advanced radiation technologies, such as proton therapy, is appropriate when needed to deliver adequate tumor doses while respecting normal tissue dose constraints 5
It is quite clear from limited studies that proton beam is not inferior to other radiotherapy techniques. What has not been proven is that it is superior and that its ability to spare the tissues translates to a better outcome. It makes sense that it should, but in science that would be called a hypothesis that needs to be proven. THis si especially so for ehad and neck, where there is less consensus than in prostate cancer. Because PBT is only available in limited centers and is much more complex and expensive than other tissue sparing radiation therapy techniques, it should still be considered investigational.
1.Y. Lievens, W. den BogaertProton beam therapy: Too expensive to become true?. Radiotherapy and Oncology, Volume 75, Issue 2, Pages 131-133 2005
2.Agency for Healthcare Research and Quality (AHRQ). Technology Assessment. Comparative
evaluation of radiation treatments for clinically localized prostate cancer: an update. August
2010. Available at: http://www.cms.gov/coveragegeninfo/downloads/id69ta.pdf.
3.Agency for Healthcare Research and Quality (AHRQ). Trikalinos TA, Terasawa T, Ip S, Raman
G, Lau J. Particle Beam Radiation Therapies for Cancer. Technical Brief No. 1. (Prepared by
Tufts Medical Center Evidence-based Practice Center under Contract No. HHSA-290-07-10055.)
Rockville, MD: AHRQ. Revised November 2009. Available at:
4.American College of Radiology (ACR). ACR Appropriateness Criteria. Nonsurgical treatment for non-small-cell lung cancer. 2010. Available at: http://www.acr.org/ac.
5.American Society for Radiation Oncology (ASTRO). Emerging Technologies Committee. An
evaluation of proton beam therapy. June 2011. Available at:
6.Blue Cross Blue Shield Association (BCBSA). Proton beam therapy for non-small-cell lung cancer. TEC Assessment, October 2010.
7.Purins A, Mundy L, Hiller J. Boron neutron capture therapy for cancer treatment. Horizon Scanning Prioritising Summary. Adelaide, SA: Adelaide Health Technology Assessment (AHTA); October 2007.
Ahmed SK et al, Protons vs Photons for Brain and Skull Base Tumors.
Semin Radiat Oncol. 2018 Apr;28(2):97-107.
Tian X, Liu K, Hou Y, Cheng J, Zhang J. The evolution of proton beam therapy: Current and future status. Mol Clin Oncol. 2017;8(1):15-21.