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Keywords:

  • medulloblastoma;
  • cost effectiveness;
  • comparative effectiveness;
  • proton;
  • Monte Carlo

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

BACKGROUND

Proton therapy has been a hotly contested issue in both scientific publications and lay media. Proponents cite the modality's ability to spare healthy tissue, but critics claim the benefit gained from its use does not validate its cost compared with photon therapy. The objective of this study was to evaluate the cost effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma.

METHODS

A cost-effective analysis was performed from the societal perspective using a Monte Carlo simulation model. A population of pediatric medulloblastoma survivors aged 18 years was studied who had received treatment at age 5 years and who were at risk of developing 10 adverse events, such as growth hormone deficiency, coronary artery disease, ototoxicity, secondary malignant neoplasm, and death. Costing data included the cost of investment and the costs of diagnosis and management of adverse health states from institutional and Medicare data. Longitudinal outcomes data and recent modeling studies informed risk parameters for the model. Incremental cost-effectiveness ratios were used to measure outcomes.

RESULTS

Results from the base case demonstrated that proton therapy was associated with higher quality-adjusted life years and lower costs; therefore, it dominated photon therapy. In 1-way sensitivity analyses, proton therapy remained the more attractive strategy, either dominating photon therapy or having a very low cost per quality-adjust life year gained. Probabilistic sensitivity analysis illustrated the domination of proton therapy over photon therapy in 96.4% of simulations.

CONCLUSIONS

By using current risk estimates and data on required capital investments, the current study indicated that proton therapy is a cost-effective strategy for the management of pediatric patients with medulloblastoma compared with standard of care photon therapy. Cancer 2013;119:4299–4307. © 2013 American Cancer Society.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Proton therapy is considered one of the most advanced modalities for radiation therapy (RT), with properties that allow for the avoidance of radiation to healthy, uninvolved tissues outside of the region that requiring radiation for tumor control.[1] By contrast, photon RT, which is more widely available, can deliver an unnecessary dose to healthy tissues, carrying with it a risk of various adverse events (Fig. 1). Reports of long-term clinical outcomes of proton RT are not yet available for most malignancies,[2] and the construction of a proton center requires a capital investment of approximately $140 million, with a cost to society of treatment for an average proton radiation course estimated at $40,000.[3, 4] Many recently published articles and editorials have addressed the lack of evidence for the cost effectiveness of proton therapy with regard to specific malignancies,[5] particularly prostate cancer. In the current health care climate, it is necessary that we closely analyze whether proton radiation truly delivers superior clinical outcomes and cost benefits compared with standard photon radiation. Despite significantly higher capital and operational costs, proton therapy may prove to be cost effective for children,[6] who are particularly susceptible to radiation-induced side effects.

image

Figure 1. These images compare (Left) proton therapy and (Right) photon therapy plans for cerebrospinal irradiation. The dose sparing anterior to the spinal column in the proton plan is evident compared with the photon plan. (Middle) The dose of radiation is delineated in centigrays according to color shade. Courtesy of Judith Adams.

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Medulloblastoma is the most common malignant cancer of the central nervous system in children, and RT is considered the standard of care for any child aged >3 years.[7] Regimens that incorporate radiation result in an overall 5-year survival rate of 75% to 85%.[8] These rates have improved substantially over the past decade.[9] Thus, as cancer survival rates have improved, the impact of treatment-related side effects has become even more important. Chronic medical problems induced by RT can impact the quality of life of these patients and are costly to families, insurers, and society. Survivors of childhood medulloblastoma are at risk of multiple adverse events because of radiation: cognitive deficits, growth hormone deficiency (GHD), ototoxicity, hypothyroidism, congestive heart failure (CHF), pulmonary disease, coronary artery disease (CAD), adrenocorticotropic hormone (ACTH) deficiency, gonadotropin deficiency, early puberty, premature ovarian failure, and radiation-induced cancers.[10] Reports have indicated that adverse events may affect >55% of survivors.[11]

The lengthy side-effect profile associated with craniospinal photon RT renders pediatric medulloblastoma an attractive malignancy for the use of proton therapy. The use of proton therapy may prevent lifelong chronic diseases through the avoidance of irradiating a large volume of normal tissue that otherwise would receive radiation and by sparing a substantial amount of brain from receiving higher doses of radiation. In addition, the high necessary capital investment in proton therapy may be reasonable considering the prolonged clinical benefits in children.[3] This amortization may make proton therapy more cost effective than conventional photon therapy. To date, only 1 cost-effective analysis (CEA) of pediatric medulloblastoma has been published—a Swedish model-based analysis that identified proton therapy as the more cost-effective strategy compared with photon therapy,[12] which was considered the standard of care. Contemporary insights into RT and risk models have provided more precise risk predictions,[7] and recently released phase 2 trial outcomes have provided primary data to enable more informed decisions.[13] With this advancement in knowledge regarding the risks and benefits associated with proton therapy, the objective of the current study was to evaluate the cost effectiveness of proton therapy compared with photon therapy in treating pediatric medulloblastoma, incorporating the best available data and costs.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

A first-order Monte Carlo simulation model of survivors of pediatric medulloblastoma was developed to evaluate the cost effectiveness of proton therapy versus photon therapy. Although we assumed that patients received treatment at age 5 years, we elected to track the health benefits and costs of individual patients starting at age 18 years to capture the health benefits throughout the adult life of surviving patients. This modeling strategy allowed for the appropriate assignment of utilities and avoided their inappropriate use for pediatric-aged patients, for whom data are scarce. Each year, individuals in the model were at risk of entering the following health states: GHD, ototoxicity, hypothyroidism, CHF, CAD, ACTH deficiency, gonadotropin deficiency, secondary malignant neoplasm (SMN), relapse, and death. Cognitive deficit was not included, because no data exist to appropriately assign a cost to an intelligence quotient (IQ) loss secondary to cranial RT. Patients had the potential to experience different health states each cycle until they reached age 100 years or experienced death. One cycle was equivalent to 1 year of time.

Each health state carried its own risk, associated utility, and cost; death could occur at any cycle because of background mortality or excess disease-specific mortality. Background annual mortality risk in the base case was derived from standard 2007 life tables.[14] Other adverse-event parameter values were identified through an extensive literature search. Proton and photon risks for ototoxicity, hypothyroidism, CHF, CAD, and SMN were derived from modeling estimates by Brodin et al.[7] Reports by Yock and colleagues[13] and Merchant et al[15] provided data to estimate the risk of GHD; the publications by Frange et al and Heikens et al informed the photon risks of ACTH deficiency and gonadotropin deficiency, respectively[16, 17]; and proton equivalents for those states were derived in concordance with the reports by Miralbell et al and Lundkvist et al.[12, 18] Health state utilities were used to reflect diminished quality of life because of disease or events and were measured on a scale from 0 (worst health state, usually death) to 1 (perfect health). The report by Sullivan and Ghushchyan provided utility values,[19] except for ACTH deficiency,[20] GHD,[21] and gonadotropin deficiency.[22]

Costs in the model included the cost of RT and the cost of managing adverse events. The cost of RT reflected the capital investment and operational management costs for working facilities and included estimates for building and infrastructure, hardware, dosimetry and engineering equipment, planning and clinical management software, and necessary licenses as well as working capital during the construction and transition phases. Salaries and benefits for physicians and staff and hospital overhead also were captured in the RT cost. These parameters were used to generate a cost per hour per room, assuming a 10-hour treatment day and a 40-year facility lifespan, excluding holidays and weekends. According to Packer et al, 31 fractions were expected, including 13 fractions of 60-minute cerebrospinal irradiation and 18 fractions of 20-minute posterior fossa boost.[23] The cost per room per hour multiplied by 19 hours of room use represented the cost for the operational and capital costs to manage 1 patient with pediatric medulloblastoma in 2012. For each incorporated health state, management strategies were determined for cost estimation from published guidelines, and these are listed in Table 1. Procedure allowables were valued using Current Procedural Terminology codes obtained from the Centers for Medicare and Medicaid Services, and specific drug management and regimen costs were calculated using the Red Book and were converted to 2012 values by using an inflation calculator from the US Department of Labor.[32, 33] The model valued health effects and costs from the societal perspective, as recommended by the US Panel on Cost Effectiveness in Health and Medicine.[34] From the same recommendation, all costs and effects were discounted at 3% per year assuming treatment at age 5 years. A diagram of the model is illustrated in Figure 2.

image

Figure 2. This diagram illustrates the possible health states (circles) a healthy survivor confronts in the model. The survivor has the potential to enter more than 1 discrete clinical state in a year: eg, the survivor has the potential to develop growth hormone deficiency (GHD) and congestive heart failure (CHF) in year 1. In this sample outcome, a patient experiences GHD during year 1, continues to persist in a GHD health state, and develops coronary artery disease (CAD) in year 2. Note that death is possible in all stages. Because of the high number of combinations, not all possibilities could be represented pictorially; the ellipses represent the other possible combinations. SMN indicates secondary malignant neoplasm.

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Table 1. Management Strategies and Sources
StateManagement StrategySource
  1. Abbreviations: 2D, 2-dimensional; ACTH, adrenocorticotropic hormone; ASA, aspirin; BUN, blood urea nitrogen; CAD, coronary artery disease; CBC, complete blood count; Cr, creatinine; CXR, chest x-ray; EKG, electrocardiogram; GHD, growth hormone deficiency; HDL, high-density lipoprotein; Hgb, hemoglobin; IGF-1, insulin-like growth factor 1; LDL, low-density lipoprotein; LFTs, liver function tests; TGs, triglycerides; TSH, thyroid-stimulating hormone; UA, urinalysis.

GHDEvery 6 mo: endocrinologist visit, serum IGF-1, and fasting glucose; annually: lipid profile; routine daily: growth hormone injectionBaskin 2009[24]
HypothyroidismAnnual TSH and free T4 test; routine daily, levothyroxineBaskin 2002[25]
OtotoxicityHearing aid with 4-y lifespan, audiometric evaluation, and telephone amplifier with 10-y lifespanMohr 2000[26]
ACTH deficiencyRoutine daily, hydrocortisoneGrossman 2010[27]
Gonadotropin deficiencyMen, daily testosterone and 6-mo serum testosterone checks; women, estradiol and medroxyprogesterone until age 50 ySnyder 2012,[28] Nelson & Calis 2012[29]
Heart failureAt diagnosis: CBC, UA, serum electrolytes with Ca and Mg, BUN, Cr, fasting blood glucose, lipid profile, LFTs, TSH, 12-lead EKG, CXR, and 2D echo with Doppler; routine daily: ramipril and chlorthalidoneHunt 2009[30]
CADAt diagnosis: rest EKG, stress EKG, Hgb, fasting glucose, and fasting lipid panel with total cholesterol, HDL, TGs, and LDL; annuals stress EKG; routine daily: ramipril, simvastatin, metoprolol, and ASAFraker 2007[41]

The model projected 2 outcome measures: lifetime costs expressed in US dollars (USD) and health benefits expressed in quality-adjusted life years (QALYs). Because each health state is associated with a particular cost and quality-of-life weight (ie, utility), a total cost and sum of QALYs could be calculated for the entire lifespan of an individual in the model, depending on time spent in each state. Owing to differing costs and risks of health states, the 2 model arms of proton therapy and photon therapy generated different sums. A quotient obtained from the difference between strategy costs divided by the difference in QALYs was used to derive an incremental cost-effectiveness ratio (ICER), which is equivalent to the incremental cost per additional QALY. The ICER can be compared with a society's generally accepted benchmark of willingness to pay (WTP) for 1 QALY. This model assumed a societal WTP of $50,000 per QALY.[35]

One-way sensitivity analyses were conducted to demonstrate the influence of parameters. In these analyses, lifetime risks were tested in the model by rerunning simulations with the proton risk equal to the photon risk. The most influential parameters identified from 1-way sensitivity analysis were selected for testing in probabilistic sensitivity analysis (PSA), in which multiple model parameters are simultaneously varied with set distributions and ranges; such analyses help illustrate the robustness of the model in light of the joint uncertainty for model parameters. Risks selected for PSA that were based on actual patient data were tested with beta distributions. Costs and risks derived from models were chosen to have uniform distributions, because those parameters were derived from models and, thus, have more uncertainty.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Base-case parameters are displayed in Table 2, and the results from a base-case analysis with 1,000,000 individual patients are provided in Table 3. The most common events for the photon arm were hearing loss and secondary cancer, and GHD and CAD were the most common for the proton arm. In the base case, proton therapy was more effective yet less costly compared with photon therapy: we defined this as proton therapy dominating photon therapy. The robustness of the base-case results was demonstrated in 1-way sensitivity analyses, as indicated in Table 4. In all scenarios, proton therapy either dominated photon therapy or was associated with a very low ICER (<$5000 per QALY).

Table 2. Base Case Model Parameters
 Health States
VariableGHDGonadotropinDeafnessHypothyroidACTHCADCHFSecond Cancer
  1. Abbreviations: ACTH, adrenocorticotropic hormone; CAD, coronary artery disease; CHF, congestive heart failure; GHD, growth hormone deficiency.

  2. a

    Values displayed for lifetime risk are for proton therapy (photon therapy).

  3. b

    After age 50 years, the model input was $1952.

  4. c

    The input costs for the first year of diagnosis were $3419 and $1394 for CAD and CHF, respectively.

Lifetime riska0.13 (0.24)0.02 (0.17)0.1 (0.62)0.08 (0.3)0.02 (0.13)0.14 (0.24)0.03 (0.09)0.07 (0.45)
Utility0.810.80350.7760.8210.910.6950.6360.795
Annual cost, $13,8232,050b1,0381583143,362c940c39,130
Table 3. Base Case Results
VariablePhoton TherapyProton TherapyDifference
  1. Abbreviations: ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

Total QALYs13.9117.373.46
Total costs, $112,789.8780,210.79−32,579.08
ICERProton dominates
Table 4. One-Way Sensitivity Analysesa
Parameter ChangeΔ EFF, QALYsΔ Cost, $ICER, $/QALY
  1. Abbreviations: ACTH, adrenocorticotropic hormone; CAD, coronary artery disease; CHF, congestive heart failure; EFF, effectiveness; GHD, growth hormone deficiency; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

  2. a

    These analyses were run with 100,000 patients. For adverse event risk testing, the risk used for protons was modified to equal the risk for photons in the base case: e.g., to test hearing loss, the proton arm value was set to 0.62, the photon arm value.

  3. b

    This value represents the estimated cost of cancer at 2 standard deviations below the average value.

  4. c

    Ratios were chosen from costing studies by Goitein & Jermann 2003[30] and Peeters 2010[3] for proton and photon therapy, respectively.

Base case3.46−32,579.08Proton dominates
Cost of second cancer, $13,005.49b3.48−30,255.36Proton dominates
Proton-to-photon cost ratioc   
×2.43.46−9931.65Proton dominates
×3.23.4717,014.134910
Risk of second cancer2.71−29,000.09Proton dominates
Risk of CAD3.22−33,542.37Proton dominates
Risk of CHF2.65−33,705.22Proton dominates
Risk of GHD3.29−16,095.94Proton dominates
Risk of hypothyroidism2.93−32,040.24Proton dominates
Risk of gonadotropin deficiency3.10−27,834.37Proton dominates
Risk of hearing loss1.75−23,042.94Proton dominates
Risk of ACTH deficiency3.36−32,259.05Proton dominates
Omission of ACTH, gonadotropin deficiency, and GHD3.458663.652510

In the sensitivity analysis, risk of hearing loss, risk of SMN, and risk of heart failure were most influential on the incremental effectiveness of proton therapy. The cost of capital investment and the risk of GHD were most influential on the incremental cost of therapy. These parameters were selected for further testing in a PSA for 25,000 patients in 1000 separate samples. A scatter plot depicting incremental cost versus incremental effectiveness for each of the 1000 runs is illustrated in Figure 3. All simulations demonstrated ICERs comparing proton and photon therapy below the WTP threshold of $50,000 per QALY. In 96.4% of the simulations, proton therapy dominated photon therapy and was cost effective in 100% of simulations.

image

Figure 3. A probabilistic sensitivity analysis is illustrated. This chart displays the results from 1000 separate simulations of 25,000 patients. In each of those separate simulations, selected risks and costs varied according to the set distributions chosen to reflect the uncertainty for those parameters. Each point represents 1 of those simulations and is charted at the simulation's resultant incremental cost versus incremental effectiveness of proton therapy compared with photon therapy. WTP indicates willingness to pay.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

This study contributes to the limited assessment of the cost effectiveness of proton therapy in the management of pediatric medulloblastoma. The results of the base case demonstrated that proton RT represents good value for money compared with photon RT. Despite the increased upfront cost of proton therapy, we observed that protons were cost saving compared with photons over the lifespan of a population of patients because of decreased costs associated with radiation-induced medical problems. These results held robust throughout 1-way sensitivity analyses and a probabilistic sensitivity analysis, in which proton therapy was a cost-effective strategy compared with photon therapy. For the 2 scenarios in which proton therapy did not dominate in 1-way analysis, its ICER fell at values less than $5000, which is well below norms for what is considered a societal WTP threshold in the United States.[35] Furthermore, the probabilistic sensitivity analysis revealed that the ICER robustly illustrated the domination of photon therapy by proton therapy in >95% of its 1000 iterations.

A notable strength of this work is its incorporation of multiple, relevant health conditions in adulthood: 10 distinct health states were modeled for patient entry. Also, costs and benefits associated with the health states were informed after an extensive review of the literature using the most recent data available on the risks and costs associated with both therapies. Furthermore, for this study, we used primary data on the cost of photon and proton capital investment. Throughout the model, the costing strategies used were conservative: the management of CAD and CHF did not incorporate high expenses, such as emergency room visits, hospitalization, or surgical intervention, which may occur throughout the natural history of disease. Instead, these strategies were modeled assuming complete pharmacologic management. Similarly, the proton strategy dominated the photon arm despite the exclusion of pediatric costs, such as special education and vocational rehabilitation associated with recently diagnosed hearing loss, which have lifetime cost estimates of $400,000 and $12,000, respectively.[26] These conservative approaches avoided overestimating health state costs and, thus, favored analysis findings toward acceptance of the photon strategy, because these events would be associated with the photon strategy with greater frequency. Consequently, findings indicating the cost effectiveness and domination of protons are more significant.

Many who argue in favor of developing proton facilities cite the domination of proton therapy over standard photon therapy in the management of childhood cancer. However, since the original publication by Lundkvist and colleagues, several assumptions may no longer hold true, and more outcomes and modeling data have been published, allowing for more precise ICER estimates.[7, 13] The former model used the same utilities to reflect the preferences of participants in pediatric and adult years of life. However, pediatric utility use for QALY determination is a frequently contested issue, and the manipulation of adult utilities for children may inappropriately reflect health effects.[36] Our study provided a novel solution to studies involving pediatric illness by focusing on adult survivors. Therefore, the model allowed for the incorporation of adult utilities for proper preference selection; and, because of the lifetime duration of the model, enough time was allowed to elapse to capture meaningful differences in QALYs gained and costs incurred. Compared with prior work, the current study expanded the health states that were included in the model to reflect a more accurate depiction of sequelae after treatment with the inclusion of ACTH deficiency, gonadotropin deficiency, and CAD. To our knowledge, this study is also the first CEA of pediatric medulloblastoma to estimate capital and investment costs from primary data, thus not only allowing for increased precision of photon costs but, even more important, allowing for a true representation of proton costs, which were further validated compared with the costs to society obtained by Peeters et al and Goitein and Jermann.[3, 37] Goitein and Jermann predicted a decrease in the proton:photon cost ratio with time, and our study's estimate corroborates that analysis. Further costing accuracy was obtained by including not only pharmacologic management costs, which had been done in former studies, but also monitoring and evaluation costs. A former review by Pijls-Johannesma and colleagues commented on the lack of a PSA in cost-effectiveness studies that evaluated proton therapy.[4] To our knowledge, this is the first CEA of pediatric medulloblastoma to incorporate a PSA in its sensitivity analysis.

It is noteworthy that, despite the incorporation of recently published data, the current study was still limited by the paucity of data available on the clinical outcomes of these patients. Premature ovarian failure, which may result from cerebrospinal irradiation, could not be included secondary to the lack of risk estimates in such patients. Early puberty was not included despite evidence from cohort studies, because its effects do not extend past adolescence and would not be captured by the model. Even so, these omitted health states would most likely incur greater average costs for photon therapy patients than for proton therapy patients because of the dose-sparing properties of proton technology. Important assumptions made were the independence of adverse events and the constant rate of disease incidence for CHF, CAD, and SMN, which may not reflect the true nature of disease. Although both GHD and ACTH deficiency can impact mortality when not properly managed, for this study, we assumed that, apart from CAD, CHF, and SMN, health states did not affect death. This decision was based on the assumption of perfect detection, management, and compliance with medication. Another limiting assumption regarded the health state of gonadotropin deficiency, which is known to affect men and women distinctly for both management and utility. However, there is no evidence suggesting that men or women have different susceptibilities to developing gonadotropin deficiency. Hence, although the study was limited in that both utilities and costs were averaged, mathematically, the analysis should be unaffected. Compared with prior work, the most notable limitation of this study was its omission of cognitive impairment, the most influential parameter in the former CEA for pediatric medulloblastoma by Lundkvist and colleagues.[12] It is probable that there is a greater loss of productivity from cognitive decline in patients who receive photon therapy; however, the use by Lundkvist et al of the cost to society per decrease in IQ score was derived from lead toxicity ecologic studies. Thus, this cost may not accurately reflect the cost of IQ loss in the setting of cranial irradiation owing to differential mechanisms of neurotoxicity and neurobehavioral outcomes.[38-40] To date, there have been no longitudinal studies detailing the cost of productivity loss secondary to cognitive decline in childhood cancer survivors managed with cranial irradiation, and that absence prompted our omission of cognitive decline as a health state to avoid inappropriate cost assignment for IQ loss. However, we can provide an estimate of the magnitude of cognitive impairment's effect on the predicted cost effectiveness of proton therapy. Similar to Lundkvist et al, we can assume that a loss of productivity secondary to cognitive impairment exists, and a subsequent cost can be estimated by the differential IQ decrement's effect on income. We can assess this cost with 2 separate methodologies to provide a range: an approach used by Schwartz and colleagues (referenced by Lundkvist et al) and 1 used by Zagorsky and colleagues.[12, 41, 42] Secondary to the 10-point IQ difference projected between groups by Merchant and colleagues,[43] there exists a differential annual wage reduction of 5% in the photon group according to Schwartz et al and of $5000 according to Zagorsky et al. Assuming a child aged 5 years today will participate in the work force from age 18 years until age 65 years, a 2% cost-of-living adjustment per year, and a 3% discounting per year, the projected cost of productivity loss is approximately $77,482 and $169,636, respectively.[40]

The objective of this study was to assess whether proton therapy is a cost-effective strategy compared with photon therapy in the management of pediatric medulloblastoma. In this study, proton therapy dominated photon therapy in the base case, but these results may differ with more accurate long-term follow-up of treated patients on current protocols. The most accurate way to determine comparative effectiveness would be a phase 3 trial comparing photons with protons in an adequately sized population; however, given the apparent dosimetric differences and the known late effects of radiation, that kind of study would be considered unethical by many. This study did not answer whether the cost effectiveness of protons in pediatric medulloblastoma translated to cost effectiveness in other malignancies and did not justify the expense of more proton facilities. The current study also did not address the cost effectiveness of including strategies with intensity modulation, such as intensity-modulated radiation therapy and intensity-modulated proton therapy, because even less clinical data are available for these modalities. Although proton therapy may dominate photon therapy in pediatric medulloblastoma, the prevalence of the disease is low and may not provide sufficient patient volume for the cost-effective use of many facilities. Future studies could elucidate the range of acceptability of proton therapy compared with photon therapy across a spectrum of malignancies, and proper phase 3 trials are needed to provide necessary risk values to inform models.

FUNDING SUPPORT

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Dr. Mailhot Vega was supported by a medical student fellowship from the American Society for Therapeutic Radiology and Oncology. The project was in part supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.

CONFLICT OF INTEREST DISCLOSURES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Dr. Tarbell's spouse serves on the medical advisory board of Procure.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES
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