Cost-Effectiveness of Proton Therapy Compared to Photon Therapy in the Management of Pediatric Medulloblastoma

Reporter: Abigail T. Berman, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 24, 2013

Presenting Author: R. Maihot Vega, MD
Presenting Author Affiliation: Washington University in St. Louis School of Medicine, Saint Louis, MO


  • Proton therapy has been an area of controversy: its ability to spare healthy tissue is counterbalanced by its high cost compared to photon therapy.
  • Medulloblastoma is pediatric tumor for which the standard treatment is resection followed by chemotherapy and craniospinal radiation. This radiotherapy is complicated by both acute adverse effects (nausea, vomiting), as well as late effects (hearing loss, endocrine abnormalities, and cardiac dysfunction). These effects should be substantially improved secondary to normal tissue sparing achieved with protons.
  • Proton therapy has been widely adapted in the United States for craniospinal radiation for medulloblastoma, and dosimetric studies have shown decreased dose to the cochlea and heart (St. Clair IJROBP 2004).
  • To date, there have been no prospective randomized trials of proton versus photon therapy for medulloblastoma.
  • The purpose of this study was to evaluate the cost-effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma.

Materials and Methods

  • A cost-effective analysis comparing proton and photon therapy from the societal perspective was performed using a first-order Monte Carlo simulation model.
  • Of note, the model assumed no difference in tumor control.
  • Actual costs used the capital and operational costs as well as the diagnostic and management costs for adverse outcomes.
  • The population was 18-year old survivors of pediatric medulloblastoma who were treated at age 5 and at risk of developing ten adverse events including growth hormone deficiency, hypothyroidism, gonadotropin deficiency, adrenocorticotropic hormone deficiency, coronary artery disease, congestive heart failure, ototoxicity, secondary malignant neoplasm, and death.
  • Costing data captured cost of investment and the diagnosis and management of adverse health states through use of primary institutional and Medicare data.
  • Longitudinal outcomes data and recent modeling studies informed risk parameters for the model.
  • With costs in 2012 USD and effectiveness measured in quality-adjusted life years (QALYs), incremental cost-effectiveness ratios were used to measure outcomes.
  • The incremental cost-effectiveness ratio (ICER) is the difference in costs divided by the differential quality adjusted life years. This value is then compared to the society's willingness to pay, i.e. how much more can be spent to gain 1 QALY.
    • A societal willingness-to-pay threshold (WTP) was assumed to be $50,000/QALY.
    • Cost-effectiveness is a binary outcome with ICER > or < willingness to pay.


  • Proton therapy was associated with higher QALYs and lower costs, and therefore dominated photon therapy.
  • In one-way sensitivity analyses, proton therapy robustly remained the more attractive strategy, either dominating photon therapy or having a very low cost per QALY gained.
  • In the sensitivity analysis, risk of hearing loss, risk of secondary malignancy, and risk of heart failure and growth hormone deficiency were most influential on the incremental effectiveness of proton therapy.
  • Cost of capital investment and risk of GHD were most influential on the incremental cost of therapy.
  • These five parameters were selected for further testing in a probabilistic sensitivity analysis (PSA). PSA results illustrated domination of proton therapy over photon therapy in 96.4% of simulations and ICERs below WTP in 100% of simulations.

Author's Conclusions

  • These data show that the use of proton therapy for the management of pediatric medulloblastoma is cost-effective, and, in most simulations, cost-saving.
  • The best way to determine cost-effectiveness is a phase III RCT, but this is unlikely to occur in this specific clinical setting.
  • This study does not answer whether the cost-effectiveness of protons in pediatric medulloblastoma translates to cost-effectiveness in other malignancies.

Clinical Implications

  • This was a well-performed study looking at cost effectiveness of protons in medulloblastoma, finding that it is indeed not only cost-effective but in fact cost-saving.
  • The authors used rigorous statistical methods to perform this analysis including first- and second-order sensitivity analyses.
  • Interestingly, risk of hearing loss, secondary malignancy, heart failure, and growth hormone deficiency were the most influential on the effectiveness of proton therapy.
  • The principal cause of bias in cost-effectiveness analysis is the lack of valid data on effects and costs, particularly in proton therapy where there is variable capital investment and operational costs.
  • While this study shows cost-effectiveness, most radiation oncologists would say that RCTs are not required for proton therapy in pediatric medulloblastoma because the benefit in reducing normal tissue toxicity in craniospinal radiation is apparent dosimetrically.
  • In addition, it has been shown in clinical data that proton craniospinal results in p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities (Brown et al. IJROBP 2013).
  • Kumar et al. (J Pediatr Hematol Oncol. 2013) also recently showed that early screening for breast cancer may be unnecessary after craniospinal with protons. This group found that when photon therapy is used for CSI, doses to the breast approach that of the Children's Oncology Group-recommended threshold, and therefore early breast cancer screening should be considered.
  • The authors appropriately note that this analysis cannot be applied to other disease sites. For example, Konski et al. (JCO 2007) showed that in prostate cancer, assuming protons could provide a 10-Gy escalation of prostate dose compared with IMRT, proton beam therapy is not cost effective for most patients with prostate cancer using the commonly accepted standard of $50,000/QALY. However, other analyses have shown cost-effectiveness.
  • This study underscores the challenges of doing cost-effectiveness studies with the appropriate sensitivity analyses; however, it supports the use of proton therapy for delivery of CSI for patients with medulloblastoma, and adds significantly to the current body of literature.


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