Table 3. Studies comparing cost of proton beam therapy and IMRT.

Study	Patients, no.	Type of study	Data source	Comparison	Cost definition	Costs included (direct vs indirect)	Perspective	Main findings including comment on risk of bias
Studies from the payer’s perspective
Konski (2007) [45]	NA	Cost modeling	Data from literature and patient interviews	Proton versus IMRT	Costs modeled in decision tree analyses (Markov model)	Direct costs	Payer’s (Medicare) perspective	70 yr old (15-yr cost) Proton cost: $63 511 (2005) IMRT cost: $36 808 (2005) Difference: $26 703 (2005) ICER: $63 578/QALY 60 yr old (15-yr cost) Proton cost: $64 989 (2005) IMRT cost: $39 355 (2005) Difference: $25 634 (2005) ICER: $55 726/QALY Model calculated cost effectiveness based on a third-party payer (Medicare) and did not include upfront costs or yearly operational costs. Sensitivity analyses included how many years the model was run, patient’s age, probability of freedom from biochemical failure for proton and IMRT, utility of patients treated with salvage hormone therapy, and treatment costs. Risk of bias high due to uncertainty of the data abstracted from the literature.
Yu (2013) [4]	553 Proton 27 094 IMRT	Retrospective cohort study	Retrospective study of Medicare beneficiaries from 2008 to 2009 (Medicare data)	Proton versus IMRT	Medicare payments	Direct costs; did not account for indirect costs, such as long travel distances for proton patients	Payer	Median Medicare reimbursement Proton: $32 428 IMRT (matched group): $18 575 Difference: $13 853 Cost of Proton and IMRT was calculated using the sum of Medicare reimbursements for all outpatient and physician claims with HCPCS codes indicative of radiotherapy, including treatment planning, management, and delivery, in the 3 mo following initiation of radiation. No adjustments for inflation, although only a 2-yr study. Used Mahalanobis matching to account for known confounders; could not use propensity score or instrumental variable analysis due to small proton numbers. Risk of bias moderate as residual confounding may be present.
Study from the societal perspective
Lundkvist (2005) [46]	NA	Cost modeling	Data from literature	Proton versus conventional (IMRT)	Costs modeled in decision tree analyses	Direct and indirect costs, including purchase cost of proton and IMRT facilities, amortization of facilities, transportation and hotel accommodations for proton patients	Societal (Sweden)	Mean proton cost: €13 491 (2002) Mean IMRT cost: €5477 (2002) Difference: €8014 (2002) The cost effectiveness of a proton facility depends on the total patient population treated (and hence the number of patients treated with different types of cancers (eg, prostate, breast, head and neck, childhood medulloblastoma). This article assumed that 300 prostate cancer patients were treated per year. The cost per QALY was about €26 776. Limitations: Information about the clinical effects of proton therapy was very limited; also lack of information on health economic data (ie, costs and QOL in patients treated with radiotherapy); as a consequence, the estimates used in the assessment had to be based on more or less uncertain assumptions. Assessment based on an assumed lifetime of 30 yr for proton facility. This could be shortened by the introduction of other new technologies or lengthened by improvements in the facilities. Risk of bias high due to uncertainty of the data abstracted from the literature.

ICER = incremental cost effectiveness ratio; IMRT = intensity-modulated radiotherapy; NA = not applicable; QALY = quality-adjusted life year; QOL = quality of life.

Note: for any cost data, the year to which inflation adjustment was made is indicated in parenthesis. Studies are listed in chronological order based on the years included in the study.