How NHS investment in proton beam therapy is coming to fruitionBMJ 2019; 364 doi: https://doi.org/10.1136/bmj.l313 (Published 11 February 2019) Cite this as: BMJ 2019;364:l313
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This article continues the important debate on the indications in which Proton Beam Therapy (PBT) can offer benefit over conventional radiotherapy.
As reported, there is evidence that PBT was oversold in the USA and this needs to be avoided as capacity for PBT grows here. The Rutherford Cancer Centres (RCC) in the UK, maintain that PBT should only be used in certain specific situations where there is clear dosimetric benefit. Indeed, we have turned down over 50% of patients referred for PBT, recommending conventional therapy in situations where the dose to critical tissues surrounding a cancer cannot be reduced by protons after double planning. Each patient is peer reviewed by our colleagues in University of Pennsylvania, one of the largest proton centres in the US, which uses similar equipment.
For decades, the UK has been left behind in its provision of PBT. Most Western European countries have had operational sites for several years. Their forward plans now call for 10-15% of radical radiotherapy to be delivered by PBT (1). The NHS plan is for less than 1.5%. This figure may well have been determined on availability and affordability but now needs review. Our first centre is open in Newport, South Wales and treating adult Welsh NHS patients following a rigorous external inspection process which included a leading US paediatric radiation oncologist. Further sites will open shortly in Northumbria, Reading, Liverpool and London.
In its own strategy document from 2012 the Department of Health document (2) states:
“There are 1500 patients in the UK per annum (including approximately 250 paediatric patients) for whom PBT is the treatment of choice with clear evidence of health gain. The cancer indications where the experts’ review of evidence identified that patients would benefit from PBT, show benefits in terms of reduced side effects, increased cure rates and reduced morbidity.”
A further document, Radiotherapy Services in England in 2012 (3), added:
"A strategic business case has been approved and there are now plans to develop a National Proton Beam Therapy Service in England delivered on two sites, the Christie and UCLH, from the end of 2017. The national service will treat up to 1500 patients annually."
Yet, despite this commitment, due to delays, no patients were treated at NHS facilities domestically prior to December 2018, and less than 250 patients were sent overseas. It is not clear what provision was made for the remaining 1250 patients who might otherwise have benefited from PBT funded by the NHS.
Meanwhile, the maximum capacity of the NHS centre in Manchester is currently 750. Whilst this is to be applauded, many NHS patients will no doubt continue to be sent overseas due to the current under-provision of PBT within the NHS.
The future is now positive for PBT in the UK, and private and public providers must cooperate as closely as possible to enhance patient outcomes. This would result in better sharing of data, research and clinical trials and could immediately end the costly and disruptive process of sending patients abroad.
Professor Karol Sikora
1. Crellin AM, Burnet NG. Proton beam therapy: the context, future direction and challenges become clearer. Clinical Oncology. 2014 Dec 1;26(12):736-8.
2. National Proton Beam Therapy Service Development Programme (Internet). Department of Health. 2012 (cited 15 February 2019). Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
3. Radiotherapy Services in England 2012 (Internet). Department of Health. 2012 (cited 15 February 2019). Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
Competing interests: I am Chief Medical Officer of Rutherford Cancer Centres.
The article by Matthew Limb (1) presents the view that an assessment of the potential benefits from expanded indications for proton therapy requires outcomes from randomised clinical trials (RCTs), being the “gold standard” methodology for assessment of therapeutic benefit from wide range of medical interventions. However in the case of proton therapy, where in most scenarios advantages in radiation dose distribution are employed to reduce the incidence or severity of long-term morbidity, running trials where the end-point may be evident decades later may well be problematic. In the case of head and neck cancer, as discussed in Limb’s article, the end-point of radiation-induced xerostomia becomes evident within the early years after treatment. On the other hand when the aim is to reduce the risk of late cardiac events decades after breast or chest wall irradiation for left sided breast cancer when the internal mammary lymph nodes also require irradiation, RCTs may not necessarily provide the only or even the optimum means of evaluating potential benefits. Although an RCT is running in North America it will be many years before results will be mature. There may be a good case for extrapolating from the data published by Darby et al (2) which reports the risk of late cardiac events in relation to the mean cardiac dose from conventional radiotherapy for which there is no low-dose threshold.
RCTs may also miss potential benefits for sub-groups, and may not be the most appropriate for picking up the rare, very late stochastic events such as radiation-induced cancers for which proton therapy is aimed at risk reduction.
The Dutch health authorities have relied heavily on a model-based approach, and have predicted an eventual requirement for proton therapy of up to 10% of irradiated patients. This model-based approach (3) involves the analysis of comparative proton and conventional x-ray plans, which in several clinical scenarios, particularly head and neck cancer, can model the benefits in terms of reduction in Normal Tissue Complication Probability (NTCP). This approach is now being explored by other groups and in additional clinical scenarios, including breast cancer (4).
It is important to remember that the current NHS England indications for proton therapy are not based on the outcomes from randomised trials. Probably the strongest consensus for the benefits of proton therapy is for the treatment of children. However the evidence comprises mainly single institution case series and planning comparisons with extrapolation of likely reduction in late effects from historic dose/response data.
Although in a number of scenarios there is a strong case for evaluating the true benefit of proton therapy using RCTs, this is not the only approach being employed internationally. The UK health administrations should employ a holistic approach to reviewing the evidence for a range of cancers with not only RCTs, but where appropriate, planning studies and model-based approaches. Continued collection of “real-world” outcome data on an international basis is also essential. Furthermore it is also important to conduct further research into the impact of health economic parameters, taking into account the cost of treating long-term complications of therapy.
1. Limb M. Where will the NHS focus its proton beam therapy plans? Br Med J 2019; 364: 253-294
2. Darby SC, Ewertz M, McGale P, et al. Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. New England Journal of Medicine 2013; 368: 987-998.
3. Langendyjk JA, Lambin P, De Ruysscher D, et al. Selection of patients for radiotherapy with protons aiming at reduction of side effects: The model-based approach. Radiotherapy and Oncology 2013; 107: 267-273
4. Vast ME, Vredeveld EJ, Credoe HM, et al. Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients. Breast Cancer Res Treat 2014; 148: 33-39
Competing interests: Clinical Advisor to Proton Partners International