Clinical trial methodology in evaluating the benefits of proton beam therapy: a systematic review


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Mercy Ofuya1,Lucy McParland2,Sarah Brown2,Louise Murray2,David Sebag-Montefiore2,Emma Hall1
1Institute of Cancer Research,2University of Leeds

Abstract

Background

Proton beam therapy (PBT) delivers high-energy radiation to target tumours while sparing surrounding normal tissues. The dosimetric advantages of PBT over photon radiotherapy are clear but there is a need to determine whether this translates into clinically meaningful reductions in side effects and improved quality of life. Randomised controlled trials (RCTs) are considered the gold standard for generating the highest level evidence in medicine. The objectives of this 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.

Method

PubMed, MEDLINE, EMBASE and Cochrane databases were systematically searched (August 2017) 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

A total of 218 studies were included. Prospective studies comprised 40% (87/218), and of these, the proportion of randomised phase II and III trials was 6% (5/87) and 5% (4/87) respectively. 72% (18/25) of phase II/III trials were conducted at a single centre. Research findings were poorly reported in over 50% of prospective studies. Over one-third of authors recommended an increase in length of follow-up. Less than 20% of studies assessed patient reported outcomes.

Conclusion

Randomised evidence for PBT is limited. The roll-out of NHS PBT services provides an opportunity for well-designed prospective studies, including RCTs, to evaluate the benefits of PBT across various disease sites.  High-quality reporting is essential for comparability and evidence synthesis. 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 optimal design of PBT studies, in addition to collection and analysis of meaningful outcome data, including quality of life and late toxicities.