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Modelling the expected increase in demand for particle radiotherapy: implications for the UK

¹ Department of Clinical Oncology, Queen Elizabeth University Hospital, Edgbaston, Birmingham B45 8TB, ² Academic Department of Radiotherapy, The Christie Hospital, Manchester, ³ University of Cambridge Department of Clinical Oncology, Oncology Centre, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ and ⁴ Northern Centre for Cancer Treatment, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK

	Abstract

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The present rapid worldwide expansion of particle radiotherapy services will inevitably have an impact on clinical practice within the UK. The most recent results of developmental trials using protons and carbon ions are impressive, with high cure rates and little or no functional normal tissue changes and a very low level of serious treatment-related morbidity. The potential numbers of patients that will demand or are referred for treatment abroad are estimated, assuming different rates of change and treatment capacities with time. Even if the maximum demand were to be under 10% of all patients presently treated by radiotherapy, significant numbers (amounting to several thousand patients per year) may be advised to seek treatment abroad between 5 and 10 years from now. The gap between overall demand and the estimated numbers could be partly, although substantially, filled by the establishment of a single large UK facility. Should demand increase beyond the estimated level, for example due to improved screening of cancer, then a network of UK particle radiotherapy centres will be required.

	Introduction

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Radiotherapy remains the most important non-surgical treatment modality for the cure of cancer; other treatment methods do not at present provide better prospects of cure [1]. These facts are likely to remain true in the foreseeable future. The pace of technological development in radiotherapy delivery has been rapid over the past 20 years, although the UK has frequently lagged behind Western Europe and North America in the implementation of new technology [2, 3]. The recent commercial availability of "turn-key" facilities for high energy particle radiation (protons and light ions such as carbon), including modern imaging and computer three-dimensional (3D) planning, represents the next stage in high precision radiotherapy.

Radioactive particles (e.g. protons and light ions) deposit ionization far more selectively, by virtue of the Bragg peak effect, than is the case with the best available megavoltage X-ray radiotherapy. These differences result in better radiation dose distributions, a marked reduction in the integral dose to normal tissues with the confident expectation of a commensurate reduction in mild and severe side effects. Dose escalation under these conditions carries the expectation of higher cure rates in cancer patients [4–8]. The importance of improved local control is reflected in the estimate that failure to achieve this results in unsuccessful treatment in about 18% of cancer patients [9].

In 1998, 15 particle facilities were operational and a similar number were in planning or construction phases [9]. There is at present a linear growth in the number of centres that can offer particle radiotherapy using either protons or light ions [10]. The distribution is worldwide, but mainly concentrated in the USA and Western Europe (for details see http://ptcog.web.psi.ch). In 2003, close to 3000 patients were treated, mostly for cancers situated in the eye. The newer facilities will enable more energetic particles to treat more deeply sited cancers in any anatomical location. High throughput in terms of patient numbers will also be possible: 2000–3000 per year is the target number in the new American centres.

The present UK Douglas-Cyclotron facility at Clatterbridge, on the Wirral peninsula, provides very successful treatment for specific sizes of malignant melanoma at appropriate positions within the conserved eye [10, 11]. Approximately 100–130 patients per year are treated using only 4 treatment exposures over 4 days. Treatment costs are of the order of £12 000 per patient. There have been unsuccessful bids for such equipment to be sited at several UK cities over the last 12 years [12]. Cost has been one restrictive issue, but the running costs are now of the same order of magnitude as complex conventional therapy, although the installation costs for cyclotrons are higher than for the conventional complex radiotherapy [11, 13].

The expansion of facilities abroad [9, 10] and the anticipated publication of the treatment outcomes in terms of high cure rates with improved quality of life will inevitably result in an increased demand that patients be referred abroad for treatment. One particularly sensitive group are children and young adults, in whom there is a tenfold reduction in the estimated risk of second cancer induction [14]. The trend for cancers to be detected at an earlier stage will continue due to the anticipated benefits of improved molecular biology (e.g. genomics, proteomics and molecular based imaging) [11, 12]. Consequently, the proportion of patients who have potentially curable cancers is likely to increase over the next decade.

This report considers the potential numbers of patients that might require particle radiotherapy in the UK or abroad in the next 20 years, with implications for planning radiotherapy services.

	Methods

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The rising capacity and demand for particle radiotherapy are considered. The following assumptions are made:

1. At present, approximately 15 patients per year are referred abroad for particle radiotherapy. The precise figure is not known because there is no central registry, but we assume one patient per 4 million population in the UK. The incremental rates are defined by the variable R; the maximum rate increase is assumed to be 100% per year with exponential kinetics (i.e. a doubling of patients in 0.693 years, since , where T_Half is the doubling time, with smaller rates that include a minimum R of 20% per year, i.e. a doubling of numbers every 3.47 years.
   
2. The growth in the numbers of international Centres and more specifically the treatment capacity at any time (K_T), will increase at approximately linear rates but growth will eventually slow down as each country achieves its target number of facilities. The maximum capacity for UK patients is defined as K_MAX.
   
3. The UK treats around 125 000 patients per year with radiotherapy. After careful comparisons of dose distributions using conventional X-rays and high energy particles, only a small proportion, just under 10%, (i.e. K_MAX=12 000 patients, are considered to be better treated by particles. This is a conservative estimate when compared with other authors [9].
   
4. The overall pattern of referrals abroad with time can be modelled by a logistic equation, where there is an apparent initial lag phase followed by pseudo-exponential, linear and a final deceleration phase (see Appendix for equations). Mathematica software (Wolfram, USA) was used to produce the graphics.
   

	Results

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We first assume that there is no immediate restriction in the capacity to accept referrals (i.e. K_T=K_MAX) and calculate the maximum numbers of patients referred abroad with time. Figure 1 shows the projected increase of patient numbers for several variations in the growth rate constant R under these conditions.

View larger version (21K): [in this window] [in a new window]   Figure 1. Estimated numbers of UK patients referred abroad per year assuming an immediate capacity elsewhere to accept all referrals up to a limit of 12 000 per year and that 15 patients annually are initially referred abroad. Variations in the rate of change parameter (R) are shown. Equation 1 is used to generate this graph (see Appendix).

Figure 2 shows how the total numbers of patients that could be treated might vary with time, assuming variable rates of change in the parameter r. The most likely value appears to be a reduction of between 2% and 4% per year in the present rate of expansion. Using a conservative value of 3% per year slowing of the increase in capacity with time, Figure 3 shows the modified numbers of patients referred abroad: these numbers are considerably smaller than those predicted at the same times in Figure 1. Even so, it shows that the UK could be sending very significant numbers of patients abroad in 5–6 years from now and that the situation would significantly deteriorate thereafter. Also, the deficit between the estimated numbers and the nominal demand level of around 12 000 per year in Figure 3 remains very significant, which would imply that thousands of patients may not obtain the best available therapy.

View larger version (21K): [in this window] [in a new window]   Figure 2. Estimated changes in international treatment capacity (KT) with time. The estimates are based on the present number of approximately 4000 patients per year worldwide. Equation 2 (see Appendix) is used to generate this graph. The rate of change of treatment capacity, r, is varied.

View larger version (22K): [in this window] [in a new window]   Figure 3. Estimated annual numbers of UK patients referred abroad and influenced by variable changes in treatment capacity (KT) with time. Variations of the growth in referral rates of 20–100% per year are shown. This graph is produced by use of Equation 1 with the capacity K replaced by the function for KT, as given in Equation 2, where the variable r is assumed to be 3% per year (see Appendix).

	Discussion

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This information, although speculative, should be of considerable interest to both purchasers and providers of health services, including the private sector, as well as Central Government. A controlled system for referral of patients abroad will require appropriate assessment and counselling from UK radiation oncology and medical physics specialists. These professional groups will require specific training that is presently unavailable in the UK. The overall economic costs (e.g. transport, accommodation and payments into foreign systems of healthcare) would be considerable and should exceed those for the same treatment given in the UK; these need to be assessed formally. There would also be significant disruption in the overall medical management within multi-disciplinary teams, social and emotional disadvantages due to the geographic separation of patients from their national environment and the established support services that exist for cancer patients in the UK, as well as the obvious linguistic and cultural differences.

The results are dependent on the validity of the logistic model. Figure 3 shows a very conservative estimate of patient numbers that might be referred abroad for two reasons. First, very conservative parameters have been used and there is no allowance for the expected extra yield of patients who have earlier diagnosis through improved screening programmes. The demand gap could therefore be much higher if, for example, 20 000–30 000 cases per year would require particle beam radiotherapy. Second, the rate of growth of international capacity may continue for a longer time at linear rates and could become supralinear with time, in which case the estimated numbers referred abroad would be between those estimated in Figures 1 and 3. It seems essential that the UK state and private healthcare systems should anticipate and prepare for these changes. Even if a decision were to be made to establish a National Particle Therapy Centre in the UK, not only would the entire process take around 4–5 years to be fully implemented, but also the national demand would only be partially met.

We have only considered the treatment of patients with relatively small cancers, who are most likely to benefit from particle irradiation. The process of particle radiotherapy may also be more efficient. For example, cure of small lung cancers in single treatment exposures, without detectable pulmonary physiological changes, has been recently achieved in Japan using carbon ion beams [10]. For more advanced tumours, combinations of chemotherapy, conventional radiotherapy and particle therapy are also showing promising results [10]. Such approaches, if confirmed, would also increase the demand for particle therapy beyond those estimated in this report.

Cost estimates for proton radiotherapy were previously estimated to be about 2.4 times higher than present complex forms of X-ray therapy, with an expectation of reduction in proton therapy costs with time [13]. Assuming the conservative estimate that only 10% of patients require proton therapy and that radiotherapy accounts for 5% of the total cost of cancer care [1], this would raise the expenditure on radiotherapy to only 5.7%. This can be compared with the cost of cytotoxic chemotherapy, which accounts for 12% of the total cancer care budget [1]. The additional initial costs for charged particle radiotherapy may be offset by reduced expenditure on the treatment of second malignancies in cured patients and on the palliation of cancers that are not cured by current techniques, thus achieving an overall cost reduction [14–16].

We recommend that further studies be performed, with full medical, social and economic costs and that at least one National Centre should be commissioned by Central Government to provide the best possible service to the UK population. This is a serious medical issue, which requires urgent attention.

	Acknowledgments and declarations of interest

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Authors BJ, PP and NGB are members of the Engineering and Physical Sciences Research Council (UK)-funded Network on the Biomedical Applications of Ion Beams. BJ is a trustee of The Cyclotron Trust (UK).

	Appendix

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The logistic equation is used to represent the increased growth of referrals as a consequence of multiple independent and competing factors (e.g. patient and physician awareness, publications of improved outcomes, willingness of authorities to finance treatments and patients to travel, a ceiling of equipment capacity and limitations of technique), where:

where N_T is the number referred at time T, K is the maximum permitted value of N (i.e. the overall treatment capacity) and R is the growth rate constant.

For a change in capacity with time (as used in Figure 3) we next assume that K will vary with time, the value then being K_T at time T so that:

where K_INIT is the initial capacity value and K_MAX is the maximum capacity value with a reduction rate constant of r.

Received for publication December 6, 2004. Accepted for publication April 14, 2005.

	References

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