Authors' recommendations: From a theoretical perspective, proton beam therapy has been explored for patients suffering from tumour growth in locations adjacent to critical anatomical structures. The procedure involves the construction of a 3D treatment plan utilising specialised software which is then relayed to the proton beam accelerator (synchrotron) where the protons will be delivered into the targeted tumour. Patients are immobilised utilising custom-made moulds to ensure accurate delivery of the radiation to the target site. The procedure is complicated and involves the use of high-tech equipment requiring input from several medical and scientific specialists. At the time of writing, over 39,000 patients have received proton therapy either alone or in conjunction with conventional radiotherapy (Levin et al. 2005).Existing comparators for proton beam therapy include external radiation therapy (IMRT etc.), internal radiation therapy (brachytherapy) and systemic radiation therapy. External radiation therapy often uses a photon energy source, such as X-rays and gamma rays. It is commonly utilised to treat various solid tumours and can be applied intraoperatively if required. Brachytherapy involves the implantation of a radiation source within the tumour to induce cell death while systemic radiation therapy involves the injection or ingestion of radioactive materials. The key disadvantage of these treatment modalities is the irradiation of healthy tissue surrounding the tumour due to the dose-distribution characteristics of conventional radiotherapy. Proton therapy could potentially be a preferable alternative to these therapies as the dose-characteristics for protons are more desirable compared to photons (refer to Figure 1).The studies included for assessment in this Horizon Scanning report were predominantly relatively small case series, with limitations in generalising the results (level IV intervention evidence). Outcome measures reported in studies include local control and survival rates, actuarial control and survival rates were calculated based on the Kaplan-Meier methodology. Complications were graded based on the LENT/SOMA scale as a measure of the severity of radiation-toxicity/side effects. Several treatment-planning studies were included that modelled the potential advantages of proton therapy to provide perspective when assessing the case series studies.The prevalence of the radiation-induced side effects in the short and long term varied quite widely across studies and appears to be within the range expected for conventional photon therapy. Several studies which utilised proton therapy exclusively suggested that protons are capable of reducing radiation-toxicity. However, the lack of consistency across the included studies and the lack of direct comparative studies severely limit the conclusiveness of these results. Ronson (2006) concluded that even with proton therapy it was still not possible to prevent visual morbidity in patients with tumours close to the optic chiasm.The regimen for proton beam therapy may impact on toxicity. For example it would appear that toxicity increased when proton and photon therapy were combined (pituitary insufficiency - Noel 2001, 2003 and Weber 2005 and endocrinological complications – Fitzek, 2006). In one study by (Bush 2002) there was a suggestion that fractionated proton therapy might reduce the risk of facial neuropathies that were apparent in two other studies with unfractionated proton therapy. However the rate of hearing preservation was low in the fractionated study and the dose applied may have been higher than necessary.Modelling studies (Lee et al. 2005, Lin et al. 2000, Miralbell et al. 2002, Miralbell et al. 1997, St.Clair et al. 2004) included within this report all concluded that proton therapy should result in substantial dose-sparing to adjacent critical structures which should translate to lower toxicity, however this has yet to be shown consistently in clinical studies.The reported local control and survival rates for patients treated with proton beam therapy were largely unconvincing due to the large variations in results. Studies on meningiomas reported improved control and survival rates when proton radiation was administered (Wenkel et al. 2000, Weber et al. 2004, Noël et al. 2002), however a clear dose-response relationship was not defined due to conflicting results. Local control and survival rates appeared to be substantially better for patients with pituitary tumours (Ronson et al. 2006, Fitzek et al. 2006) however the outcomes for other head and neck tumours were largely inconclusive. Based on current evidence, it is difficult to state if proton beam therapy results in improved local tumour control and/or survival rates.The cost-effectiveness studies on proton beam therapy revealed that proton beam therapy will continue to be more expensive compared to conventional X-ray/photon therapy despite future assumptions of cost reductions (Goitein and Jermann 2003). This is predominantly related to substantial capital costs, and the costs of operating the synchrotron.There are a substantial number of studies of proton beam therapy for the treatment of neoplasms involving, or adjacent to, cranial structures. However, they varied in treatment methodology, only included small numbers of patients, did not use a concurrent control and used different methodologies for capturing adverse event information. Hence the results are largely inconclusive and further investigations are required to establish if proton beam therapy offers the safety advantages purported by numerous model/treatment-planning studies. Such studies should determine the optimal dosing regimen for each type of tumour including whether it should be used in combination with proton therapy and in what form (e.g. unfractionated). In addition, long-term comparative studies are required to determine if proton therapy results in increased local control rates and survival rates compared to conventional radiotherapy.

Project Status: Completed

URL for project: http://www.horizonscanning.gov.au/internet/horizon/publishing.nsf/Content/211ABF81A69CA39DCA2575AD0080F3DC/$File/HSR%20-%20proton%20beam%20therapy%20(neoplasms%20intracranial).pdf

Year Published: 2007

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Australia

Organisation Name: Australian Safety and Efficacy Register of New Interventional Procedures-Surgical

Contact Address: ASERNIP-S 24 King William Street, Kent Town SA 5067 Australia Tel: +61 8 8219 0900

Contact Name: racs.asernip@surgeons.org

Contact Email: racs.asernip@surgeons.org

Copyright: Australian Safety and Efficacy Register of New Interventional Procedures - Surgical (ASERNIP-S)