Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. RESULTS: The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. CONCLUSIONS: Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Proton facility economics: the importance of "simple" treatments.

PURPOSE: Given the cost and debt incurred to build a modern proton facility, impetus exists to minimize treatment of patients with complex setups because of their slower throughput. The aim of this study was to determine how many "simple" cases are necessary given different patient loads simply to recoup construction costs and debt service, without beginning to cover salaries, utilities, beam costs, and so on. Simple cases are ones that can be performed quickly because of an easy setup for the patient or because the patient is to receive treatment to just one or two fields. METHODS: A "standard" construction cost and debt for 1, 3, and 4 gantry facilities were calculated from public documents of facilities built in the United States, with 100% of the construction funded through standard 15-year financing at 5% interest. Clinical best case (that each room was completely scheduled with patients over a 14-hour workday) was assumed, and a statistical analysis was modeled with debt, case mix, and payer mix moving independently. Treatment times and reimbursement data from the investigators' facility for varying complexities of patients were extrapolated for varying numbers treated daily. Revenue assumptions of $X per treatment were assumed both for pediatric cases (a mix of Medicaid and private payer) and state Medicare simple case rates. Private payer reimbursement averages $1.75X per treatment. The number of simple patients required daily to cover construction and debt service costs was then derived. RESULTS: A single gantry treating only complex or pediatric patients would need to apply 85% of its treatment slots simply to service debt. However, that same room could cover its debt treating 4 hours of simple patients, thus opening more slots for complex and pediatric patients. A 3-gantry facility treating only complex and pediatric cases would not have enough treatment slots to recoup construction and debt service costs at all. For a 4-gantry center, focusing on complex and pediatric cases alone, there would not be enough treatment slots to cover even 60% of debt service. Personnel and recurring costs and profit further reduce the business case for performing more complex patients. CONCLUSIONS: Debt is not variable with capacity. Absent philanthropy, financing a modern proton center requires treating a case load emphasizing simple patients even before operating costs and any profit are achieved.

[Is proton beam therapy the future of radiotherapy? Part I: clinical aspects]. / La protonthérapie: avenir de la radiothérapie? Première partie: aspects cliniques.

Proton beam therapy uses positively charged particles, protons, whose physical properties improve dose-distribution (Bragg peak characterized by a sharp distal and lateral penumbra) compared with conventional photon-based radiation therapy (X-ray). These ballistic advantages apply to the treatment of deep-sited tumours located close to critical structures and requiring high-dose levels. [60-250 MeV] proton-beam therapy is now widely accepted as the "gold standard" in specific indications in adults--ocular melanoma, chordoma and chondrosarcoma of the base of skull --and is regarded as a highly promising treatment modality in the treatment of paediatric malignancies (brain tumours, sarcomas…). This includes the relative sparing of surrounding normal organs from low and mid-doses that can cause deleterious side-effects such as radiation-induced secondary malignancies. Other clinical studies are currently testing proton beam in dose-escalation evaluations, in prostate, lung, hepatocellular cancers, etc. Clinical validation of these new indications appears necessary. To date, over 60,000 patients worldwide have received part or all of their radiation therapy program by proton beams, in approximately 30 treatment facilities.

On the cost-effectiveness of Carbon ion radiation therapy for skull base chordoma.

AIM: The cost-effectiveness of Carbon ion radiotherapy (RT) for patients with skull base chordoma is analyzed. MATERIALS AND METHODS: Primary treatment costs and costs for recurrent tumors are estimated. The costs for treatment of recurrent tumors were estimated using a sample of 10 patients presenting with recurrent chordoma at the base of skull at DKFZ. Using various scenarios for the local control rate and reimbursements of Carbon ion therapy the cost-effectiveness of ion therapy for these tumors is analyzed. RESULTS: If local control rate for skull base chordoma achieved with carbon ion therapy exceeds 70.3%, the overall treatment costs for carbon RT are lower than for conventional RTI. The cost-effectiveness ratio for carbon RT is 2539 Euro per 1% increase in survival, or 7692 Euro per additional life year. CONCLUSION: Current results support the thesis that Carbon ion RT, although more expensive, is at least as cost-effective as advanced photon therapies for these patients. Ion RT, however, offers substantial benefits for the patients such as improved control rates and less severe side effects.

A systematic literature review of the clinical and cost-effectiveness of hadron therapy in cancer.

BACKGROUND: In view of the continued increase in the number of hadron (i.e. neutron, proton and light or heavy ion) therapy (HT) centres we performed a systematic literature review to identify reports of the efficacy of HT. METHODS: Eleven databases were searched systematically. No limit was applied to language or study design. Established experts were contacted for unpublished data. Data on outcomes were extracted and summarised in tabular form. RESULTS: Seven hundred and seventy three papers were identified. For proton and heavy ion therapy, the number of RCTs was too small to draw firm conclusions. Based on prospective and retrospective studies, proton irradiation emerges as the treatment of choice for some ocular and skull base tumours. For prostate cancer, the results were comparable with those from the best photon therapy series. Heavy ion therapy is still in an experimental phase. CONCLUSION: Existing data do not suggest that the rapid expansion of HT as a major treatment modality would be appropriate. Further research into the clinical and cost-effectiveness of HT is needed. The formation of a European Hadron Therapy Register would offer a straightforward way of accelerating the rate at which we obtain high-quality evidence that could be used in assessing the role of HT in the management of cancer.

Catching the proton wave.

Proton therapy is hailed as a huge leap in treating certain cancers. But hospitals that want proton centers need deep pockets, lots of land and the right staff.

Permanent prostate brachytherapy: is supplemental external-beam radiation therapy necessary?

Permanent prostate brachytherapy with or without supplemental therapies is a highly effective treatment for clinically localized prostate cancer, with biochemical outcomes and morbidity profiles comparing favorably with competing local modalities. However, the absence of prospective randomized brachytherapy trials evaluating the role of supplemental external-beam radiation therapy (XRT) has precluded the development of evidence-based treatment algorithms for the appropriate inclusion of such treatment. Some groups advocate supplemental XRT for all patients, but the usefulness of this technology remains largely unproven and has been questioned by recent reports of favorable biochemical outcomes following brachytherapy used alone in patients at higher risk. Given that brachytherapy can be used at high intraprostatic doses and can obtain generous periprostatic treatment margins, the use of supplemental XRT may be relegated to patients with a high risk of seminal vesicle and/or pelvic lymph node involvement. Although morbidity following brachytherapy has been acceptable, supplemental XRT has shown an adverse impact on long-term quality of life. The completion of ongoing prospective randomized trials will help define the role of XRT as a supplement to permanent prostate brachytherapy.

The case for particle therapy.

Among the most important decisions facing the British Government regarding the treatment of cancer in the National Health Service (NHS) is the purchase of charged particle therapy (CPT) centres. CPT is different from conventional radiotherapy: the dose is deposited far more selectively in Bragg Peaks by either protons or "heavy" ions, such as carbon. In this way, it is possible to "dose paint" targets, voxel by voxel, with far less dose to surrounding tissues than with X-ray techniques. At present the UK possesses a 62 MeV cyclotron proton facility at Clatterbridge (Wirral), which provides therapy for intraocular cancers such as melanoma; for deeper situated cancers in the pelvis, chest etc., much higher energies, over 200 MeV are required from a synchrotron facility. There is an impressive expansion in particle beam therapy (PBT) centres worldwide, since they offer good prospects of improved quality of life with enhanced cancer cures in situations where conventional therapy is limited due to radioresistance or by the close proximity of critical normal tissues. There is a threat to UK Oncology, since it is anticipated that several thousand British patients may require referral abroad for therapy; this would severely disrupt their multidisciplinary management and require demanding logistical support.

The relative costs of proton and X-ray radiation therapy.

AIM: To study the costs of intensity-modulated proton therapy and intensity-modulated X-ray therapy with the particular goal of understanding their relative differences. To analyse the ratio of the cost per fraction of proton therapy to the cost per fraction of X-ray therapy. MATERIALS AND METHODS: We have used a computer spreadsheet tool in which a large number (typically 130) of input parameters characterizing a particular therapeutic modality can be stored. From these parameters a number of derived variables are computed, and from these derived variables the costs of sub-systems, the entire facility, running costs and cost per fraction and per treatment can be computed. The sensitivity of any given variable (e.g. cost/fraction) to any given parameter (e.g. set-up time) can be explored, together with an estimate of the associated confidence interval. The costs of facility construction and facility operation are considered separately. Key data for the input variables regarding the cost of the therapy equipment (a dominant cost for proton beam therapy) were provided by four commercial vendors. Other costs, such as costs for building construction and shielding or personnel costs, are much more standard and our estimates were primarily based on practical experience. We considered two scenarios: (1) both facilities operating under current conditions; and (2) future facilities where foreseeable improvements in efficiency and a 25% reduction in the cost of the proton equipment were assumed. RESULTS: The construction cost of a current two-gantry proton facility, complete with the equipment, was estimated at 62,500 kEE and of a two-linac X-ray facility at 16,800 kEE. In the case of proton therapy the cost of operation of the facility was found to be dominated, by the business cost (42%--primarily the cost of repaying the presumed loan for facility construction), personnel costs (28%) and the cost of servicing the equipment (21%). For X-ray therapy, the cost of operation was seen to be dominated by the personnel cost (51%) and the business costs (28%). The costs per fraction were estimated to be 1.025 kEE for protons and 0.425 kEE for X-rays--for a ratio of costs of 2.4 +/- 0.35 (85% confidence). In a future facility these costs could be reduced to 0.65 kEE and 0.31 kEE respectively, leading to a ratio of costs of 2.1. A number of further improvements could be imagined which could reduce the ratio of costs by some 20%. If, however, the initial capital investment were 'forgiven,' so that the operating costs need not repay the investment, both the costs and the ratio of costs would be significantly less. We estimate that, under this condition, the future costs of proton and X-ray therapies would be 0.37 kEE and 0.23 kEE, respectively, for a cost-per-fraction ratio of 1.6. This ratio could also be susceptible to a further 20% reduction. CONCLUSIONS: Sophisticated (i.e., intensity-modulated) proton therapy is now, and is likely to continue to be, more expensive than sophisticated (i.e., intensity-modulated) X-ray therapy. The ratio of costs is about 2.4 at present and could readily come down to 2.1, and even, perhaps 1.7 over the next 5 to 10 years. If recovery of the initial investment is not required, the ratio of costs would be much lower, in the range of 1.6 to 1.3. The question of whether the greater cost of proton beam therapy is clinically worthwhile is a cost-effectiveness issue. The goal of this study is to contribute to the former arm of this comparison.