Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jul 12:19:17-26.
doi: 10.1016/j.ctro.2019.07.002. eCollection 2019 Nov.

Systematic review of methodology used in clinical studies evaluating the benefits of proton beam therapy

Affiliations

Systematic review of methodology used in clinical studies evaluating the benefits of proton beam therapy

Mercy Ofuya et al. Clin Transl Radiat Oncol. .

Abstract

Background: Proton beam therapy (PBT) delivers high-energy radiation to target tumours while sparing surrounding normal tissues. The dosimetric advantages of PBT over traditional photon radiotherapy may be clear but the translation of this benefit into clinically meaningful reductions in toxicities and improved quality-of-life (QoL) needs to be determined. Randomised controlled trials (RCTs) are considered the gold standard for generating the highest-level evidence in medicine. The objectives of this systematic review were to provide an overview of published clinical studies evaluating the benefits of PBT, and to examine the methodology used in clinical trials with respect to study design and outcomes.

Methods: PubMed, EMBASE and Cochrane databases were systematically searched for published clinical studies where PBT was a cancer treatment intervention. All randomised and non-randomised studies, prospective or retrospective, were eligible for inclusion.

Results: In total, 219 studies were included. Prospective studies comprised 89/219 (41%), and of these, the number of randomised phase II and III trials were 5/89 (6%) and 3/89 (3%) respectively. Of all the phase II and III trials, 18/24 (75%) were conducted at a single PBT centre. Over one-third of authors recommended an increase in length of follow up. Research design and/or findings were poorly reported in 74/89 (83%) of prospective studies. Patient reported outcomes were assessed in only 19/89 (21%) of prospective studies.

Conclusions: Prospective randomised evidence for PBT is limited. The set-up of national PBT services in several countries provides an opportunity to guide the optimal design of prospective studies, including RCTs, to evaluate the benefits of PBT across various disease sites. Collaboration between PBT centres, both nationally and internationally, would increase potential for the generation of practice changing evidence. There is a need to facilitate and guide the collection and analysis of meaningful outcome data, including late toxicities and patient reported QoL.

Keywords: Clinical trial methodology; Patient reported outcomes; Proton beam therapy; Randomized controlled trials; Systematic review.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flowchart of search strategy in accordance with PRISMA statement. Abbreviations: PBT Proton beam therapy; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Fig. 2
Fig. 2
Distribution of prospective and retrospective studies by year of publication (n = 219).
Fig. 3
Fig. 3
Distribution of study designs used in included studies.
Fig. 4
Fig. 4
Distribution of disease sites in adult and paediatric patients (n = 188). Abbreviation: CNS = Central nervous system.
Fig. 5
Fig. 5
Distribution of phase II and III trials by disease site treated by PBT (n = 24). Abbreviation: CNS = Central nervous system.
Fig. 6
Fig. 6
Distribution of geographical location of PBT treatment centre (n = 219). Abbreviation: PBT = Proton beam therapy.

Similar articles

Cited by

References

    1. Fuss M., Hug E.B., Schaefer R.A. Proton radiation therapy (prt) for pediatric optic pathway gliomas: comparison with 3d planned conventional photons and a standard photon technique. Int J Radiat Oncol Biol Phys. 1999;45(5):1117–1126. - PubMed
    1. Archambeau J.O., Slater J.D., Slater J.M., Tangeman R. Role for proton beam irradiation in treatment of pediatric cns malignancies. Int J Radiat Oncol Biol Phys. 1992;22(2):287–294. - PubMed
    1. Lin R., Hug E.B., Schaefer R.A., Miller D.W., Slater J.M., Slater J.D. Conformal proton radiation therapy of the posterior fossa: a study comparing protons with three-dimensional planned photons in limiting dose to auditory structures. Int J Radiat Oncol Biol Phys. 2000;48(4):1219–1226. - PubMed
    1. Yock T., Schneider R., Friedmann A., Adams J., Fullerton B., Tarbell N. Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons. Int J Radiat Oncol Biol Phys. 2005;63(4):1161–1168. - PubMed
    1. MacDonald S.M., Safai S., Trofimov A. Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. Int J Radiat Oncol Biol Phys. 2008;71(4):979–986. - PubMed