Technology in Cancer Research and Treatment

ISSN 1533-0346
Volume 15 Number 1 February 2016
2014 April 16. Epub ahead of print.

The Technique, Resources and Costs of Stereotactic Waseem Sharieff, M.D.,

Body Radiotherapy of Prostate Cancer: Ph.D.1-4*
A Comparison of Dose Regimens and Jeffrey N. Greenspoon, M.D.,
Delivery Systems M.Sc.1,2
Ian Dayes, M.D., M.Sc.1,2
www.tcrt.org Tom Chow, Ph.D.1,2
DOI: 10.7785/tcrt.2012.500431
James Wright, M.Sc., M.D.1,2
Robotic system has been used for stereotactic body radiotherapy (SBRT) of prostate cancer. Himu Lukka, M.B., Ch.B.1,2
Arc-based and fixed-gantry systems are used for hypofractionated regimens (10-20 ­fractions)
and the standard regimen (39 fractions); they may also be used to deliver SBRT. Studies are
currently underway to compare efficacy and safety of these systems and regimens. Thus, we
1
Department of Radiation Oncology,
describe the technique and required resources for the provision of robotic SBRT in relation to Juravinski Cancer Centre, Hamilton
the standard regimen and other systems to guide investment decisions. Using administrative
Health Sciences, Hamilton, ON, Canada
data of resource volumes and unit prices, we computed the cost per patient, cost per cure
and cost per quality adjusted life year (QALY) of four regimens (5, 12, 20 and 39 fractions)
2
Department of Oncology, McMaster
and three delivery systems (robotic, arc-based and fixed-gantry) from a payer’s perspective. University, Hamilton, ON, Canada
We performed sensitivity analyses to examine the effects of daily hours of operation and 3
Department of Medicine, Division
in-room treatment delivery times on cost per patient. In addition, we estimated the budget
impact when a robotic system is preferred over an arc-based or fixed-gantry system. Costs of Oncology, Cape Breton Regional
of SBRT were $6333/patient (robotic), $4368/patient (arc-based) and $4443/patient (fixed- Cancer Centre, Sydney, NS, Canada
gantry). When daily hours of operation were varied, the cost of robotic SBRT varied from 4
Department of Radiation Oncology,
$9324/patient (2 hours daily) to $5250/patient (10 hours daily). This was comparable to the
costs of 39 fraction standard regimen which were $5935/patient (arc-based) and $7992/ Dalhousie University, Halifax,
patient (fixed-gantry). In settings of moderate to high patient volume, robotic SBRT is cost NS, Canada
effective compared to the standard regimen. If SBRT can be delivered with equivalent
efficacy and safety, the arc-based system would be the most cost effective system.

Key words: Cost effectiveness; Hypofractionation; Prostate cancer; Stereotactic body

radiotherapy.

Introduction

The positive results of dose escalation studies with external beam radiotherapy in
the treatment of low and intermediate risk prostate cancer led to the adoption of
a high dose regimen as the standard (1-3). This regimen usually comprises of a
total dose of 78 Gy delivered in 39 fractions in an 8-week course. ­Radiobiologic
models suggest that tumor control may be further improved by adopting

Abbreviations: 3D: Three Dimensional; bNED: Biochemical Non-evidence of Disease; CT:

Computed Tomography; CTV: Clinical Target Volume; DRR: Digitally Reconstructed Radiograph; *Corresponding author:
FEISTA: Fast Imaging Employing Steady State Acquisition; IMRT: Intensity Modulated Radio- Waseem Sharieff, M.D., Ph.D.
therapy; MRI: Magnetic Resonance Imaging; OHIP: Ontario Health Insurance Plan; PSA: Prostate Phone: (902) 567 8074
Specific Antigen; PTV: Planning Target Volume; QALY: Quality Adjusted Life Year; SBRT: Stereo- Fax: (902) 567 8075
tactic Body Radiotherapy; T: Tumor Size; T2: Transverse Relaxation Time. E-mail: doc.sharieff@utoronto.ca

171
172
hypofractionated regimens (4-6). Hypofractionated regimens
deliver higher dose/fraction in a relatively short course (5-20
fractions in 2-4 weeks), compared to the standard regimen.
Recently, high precision techniques have become available
that allow safe delivery of hypofractionated regimens. This
has resulted in a growing interest in such regimens which
may be delivered by arc-based or fixed-gantry systems; ultra-
hypofractionated regimens (5 fractions) may be better deliv-
ered through robotic systems using stereotactic techniques (7).
There are promising short term data on patients’ outcome for
a 5 fraction regimen treated on a robotic system (8, 9). Fur-
ther research is underway in which arc-based and fixed-gantry
systems are also being used to deliver ultra-­hypofractionated
regimen (10).
Due to relatively short courses and the use of state-of-the-art
high precision technology, hypofractionated regimens appear
attractive. However, robotic systems are more expensive and
they are dedicated to stereotactic treatments only. Thus, they
are available in few centres. They require up to 60 minutes
for treatment delivery (6). In comparison, arc-based systems
can deliver stereotactic and standard treatments with a rela-
tively short delivery time. Thus, they are becoming increas-
ingly available. Therefore, we performed an economic
evaluation of robotic system in comparison to arc-based and
fixed-gantry systems for the treatment of prostate cancer to
guide investment decisions in these technologies.
Methods
Population
The population comprised of adult male patients with low
risk prostate cancer (T # 2a, Gleason score # 6, prostate
specific antigen (PSA) # 10 ng/ml). Using Monte Carlo
methods, we simulated a cohort of 5000 male patients aged
70  10 years.
Comparisons
We compared 3 delivery systems: (a) Robotic; (b) Arc-based
and (c) Fixed-gantry, in the treatment of prostate cancer
using 3 hypofractionation regimens compared to the stan-
dard. The hypofractionation regimens were: (i) 36.25 Gy,
7.25 Gy/fraction, 5 fractions; (ii) 51.6 Gy, 4.3 Gy/fraction, 12
fractions and (iii) 60 Gy, 3 Gy/fraction, 20 fractions. We used
78 Gy, 2 Gy/fraction, 39 fractions as the reference standard.
Stereotactic Body Radiotherapy (SBRT)
Stereotaxis refers to a precise three-dimensional (3D) map-
ping technique to guide a procedure. SBRT refers to stereo-
tactically guided conformal irradiation of a defined target
volume (at any site except the brain) with a high dose (.7 Gy)
Technology in Cancer Research & Treatment 2014 April 16. Epub ahead of print
Sharieff et al.
per fraction in 3-8 fractions. Other fractionation schemes that
deliver higher dose per fraction compared to the standard
regimen are simply referred to as hypofractionated regimens.
Robotic SBRT
At our centre, Cyberknife® is used for robotic SBRT. A
prostate cancer patient is first referred to an interventional
radiologist for the insertion of 4 gold seeds (fiducials)
into the prostate. Accuray® recommends a minimum of 4
fiducials to account for fiducial migration. After insertion
of these fiducials, the patient is brought back for an MRI of
the prostate. Prostate is examined using slice thickness of
1 mm. The patient is instructed to come for a CT simulation
with comfortably full bladder and empty rectum. Laxatives
may be given to empty the rectum. At the time of simula-
tion, Radiation Therapists position the patient supine. Next,
they perform a CT simulation with slice thickness of 1 to
1.5 mm. After the images are exported to the planning soft-
ware, a dosimetrist performs a fusion between simulation CT
and the MRI (T2 FEISTA). The dosimetrist also sets up a
reference point called ‘alignment centre’ on the simulation
CT (Figure 1A). The Radiation Oncologist delineates the
Figure 1: Stereotactic body radiotherapy. (A) The alignment center on an
axial plane for a robotic SBRT plan. (B) Schematically shows a robotic
radiosurgery unit. The ovals are the cameras located on the ceiling, arrows
represent the KV beams intersecting at the imaging center, rectangles at the
bottom are the image detectors located on the floor, rectangle at the center
represents the couch on which the patient is positioned. Note that the align-
ment center over the couch is aligned to the imaging center which provides
the external 3D coordinates. (C) and (D) Diagrammatically show arc-based
or fixed-gantry SBRT. (C) Shows the position of prostate (solid) in relation
to the 3D planes (arrows). (D) Shows various cut levels in a cone beam CT
scan (upper left); upper right and bottom sub-panels show overlay of cone
beam CT (dotted) on simulation CT (solid) in all 3 planes. Note that the
seeds shown on simulation CT and external contours of the prostate are
matched to the corresponding seeds and contours on cone beam CT in all 3
planes. If an acceptable match is not apparent, the patient is shifted/rotated
and cone beam CT images are re-acquired until an acceptable match is
obtained.
Economics of Prostate Radiotherapy
clinical target volume (CTV) and organs at risk. CTV com-
prises of the entire prostate; organs at risk include the pros-
tatic urethra, bladder, rectum and femoral heads among
others. The dosimetrist geometrically expands CTV by 5 mm
to planning target volume (PTV); where the CTV is abutting
an organ-at-risk (i.e., the rectum), CTV to PTV expansion
is 3 mm. The dosimetrist generates a plan in which 300-400
beams from various directions and path lengths traverse the
PTV. The dose is prescribed to the isodose line that cov-
ers 95% of the PTV, which is typically $80% isodose line
(when the plan is normalized to maximum point dose). This
results in .100% of the prescription dose in the centre of the
PTV, and in a steep dose gradient outside the PTV wherein
the dose rapidly falls off. The dose to the prostatic urethra
is constrained to ,107% and the entire CTV is covered by
100% of the prescription dose. The Physicist reviews the plan
and the Radiation Oncologist approves it. The planning sys-
tem generates 2 sets of digitally reconstructed radiographs
(DRRs) for alignment and for tracking fiducials.
At the time of treatment delivery, therapists position and
immobilize the patient as before. The alignment centre on the
reference DRRs is aligned to the imaging centre. The imag-
ing centre provides the 3D coordinates for stereotaxis. It is a
point in space in the treatment unit which is intersected by 2
orthogonal kilovoltage beams from the two cameras located
on the ceiling – 2 image detectors located on the opposite
side of the floor detect these beams (Figure 1B). These cam-
eras continuously take images in real time which are matched
to the reference DRRs for target localization. The robot on
which the linear accelerator is mounted, corrects for any
misalignment at the time of set up and during the course of
treatment delivery.
Arc-based SBRT
Our centre uses a Varian Trilogy® linac. The therapists posi-
tion the patient supine and immobilize the pelvis. The rest of
the planning is similar except that arcs are used for PTV cov-
erage. MRI acquisition and fusion is not routinely performed
and thus, dose to the entire PTV (including the prostatic
urethra) is constrained to ,107% of the prescription dose.
At the time of treatment delivery, the therapists set up the
patient as before. They use a cone beam CT scanner which
is attached to the linear accelerator to acquire set-up images.
They match the images by overlaying them on the planning
CT (Figure 1D). If unacceptable, the therapists manually
shift and or rotate the patient to correct the misalignment.
They re-acquire the cone beam CT images for matching until
an acceptable match is obtained. The linear accelerator deliv-
ers radiation to the lesion. Arc-based treatments are planned
and delivered using dynamic conformal multi-leaf collima-
tors in 1 to 2 arcs.
Technology in Cancer Research & Treatment 2014 April 16. Epub ahead of print
173
Fixed-gantry Based SBRT
The set up and treatment delivery is similar to arc-based
SBRT. The only difference is instead of 1-2 arcs for treat-
ment delivery, the fixed-gantry SBRT uses 7 coplanar beams.
Type of Evaluation and Perspective
We carried out a cost effectiveness analysis of treating low
risk prostate cancer with SBRT and hypofractionation regi-
mens compared to the standard using robotic, arc-based
and fixed-gantry systems from a payer’s perspective. This
involved calculating cost per patient, cost per cure and cost
per quality adjusted life year (QALY) for each regimen and
each system, and incremental costs of robotic SBRT com-
pared to the standard regimen with fixed-gantry. In addition,
we calculated the incremental budget impact of acquiring a
robotic system compared to a fixed-gantry system.
The Model
The starting point of the model was a fictitious cohort of
patients assigned to robotic system, arc-based system, or to
Fixed-gantry system. With the exception of the robotic sys-
tem, each system was assigned to one of the four radiation
regimens; robotic system was assigned to the 5 fraction regi-
men only (Figure 2). The patients underwent initial clinical
assessment, treatment planning and treatment delivery. They
were seen in review clinic on a weekly basis during radiation
treatment and at six weeks post treatment. Thereupon, they
were seen bi-annually for 5 years with PSA measurements at
each visit. They were then discharged to be followed by their
family physicians.
Assumptions
We assumed that: (1) all systems were equally effective and
equally safe (11); (2) patients’ average life expectancy was
20 years (min-max: 5-35 years); (3) arc-based and fixed-
gantry systems would operate 10 hours daily for 5 days a
week and treat all disease sites (including stereotactic and
standard regimens); (4) robotic system would operate for
6 hours daily for 5 days a week and would only deliver
stereotactic regimens to disease sites including brain, spine,
lung, prostate and pancreas (5) and each system would be
acquired through a bank loan at 5% interest rate and an amor-
tization period of 10 years.
Data Sources
We compiled a list of resources associated with each sys-
tem and treatment regimen. One of the authors (WS) directly
observed and estimated mean (and min-max) values for sim-
ulation, planning and treatment delivery times. We defined
174 Sharieff et al.

Figure 2: Model comparisons. The model compares four external beam radiotherapy regimens (5, 12, 20 and 39 fractions) and three treatment delivery
systems (robotic, arc-based and fixed-gantry based) for the treatment of low risk prostate cancer in a 70 years old male. Note that robotic system is only used
for ultra-hypofractionation also known as stereotactic body radiotherapy (SBRT).

Table I
Resource volumes.

Resource volumes Fixed-gantry Arc Robotic

Clinic visit1
Radiation Oncologist 1 1 1
Nurse 1 1 1
  Consultation 1 1 1
  Review Weekly Weekly Weekly
Follow up Bi-annually Bi-annually Bi-annually
Preparation
Fiducials Yes Yes Yes
MRI 1 1 1
Simulation2
Radiation Therapist(s) 3 3 3
Time (min/patient) 10 10 10
Planning3
Radiation Oncologist 1 1 1
Physicist 1 1 1
Time (min/patient) 60 60 60
Radiation Therapist(s) 1 1 1
Time (min/patient) 300 300 300
Delivery4
Physicist 1 1 1
Radiation Therapist(s) 3 3 3
  Time (min/patient)
    5 fraction regimen (SBRT) 30 28 45
   12 fraction regimen 25 12 NA
   20 fraction regimen 20 10 NA
   39 fraction regimen 15 8 NA
QA5
Physicist 1 1 1
Time (hr/year) 509 509 608
1
One consultation, one review, and one follow up visit.
2
Immobilization and CT simulation.
3
Target volume and organ at risk delineation, beam arrangement, dose computation, revisions and DRR generation.
4
Total in-room time for stereotactic radiotherapy (set up and alignment, target tracking and treatment, image verification).
5
QA: quality assurance (12).

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Economics of Prostate Radiotherapy 175

Table II
Costs.

Unit price Fixed-gantry Arc Robotic Source

Radiation Oncologist fee/consult $152.40 $152.40 $152.40 OHIP (13)

Radiation Oncologist fee/review $37.05 $37.05 $37.05 OHIP (13)
Radiation Oncologist fee/follow up $68.90 $68.90 $68.90 OHIP (13)
Radiation Oncologist fee/plan $811.15 $811.15 $811.15 OHIP (13)
Radiation Therapist salary/hr $52.00 $52.00 $52.00 Sharieff et al. (12)
Physicist salary/hr $94.00 $94.00 $94.00 Sharieff et al. (12)
Nurse salary/hr $50 $50 $50 Sharieff et al. (12)
MRI/plan $1,000 $1,000 $1,000 Sharieff et al. (12)
Overhead
Annual payment1 machine  installation $476,235.84 $476,235.84 $622,191.84 Sharieff et al. (12)
Annual maintenance $8,580 $8,580 $14,400 Sharieff et al. (12)

OHIP: Ontario Health Insurance Plan (13).

Based on 5% interest rate and 10 years amortization period.
1

in-room treatment times as the time the treatment unit was
occupied by the patient, and we obtained these times from
our centre’s administrative database. In-room time includes
time for set up, image verification and treatment delivery.
Table I shows resources.
For unit prices of the resources, we used our centre’s purchase
data (12) and Ontario Health Insurance Plan (OHIP) billing
codes where applicable (13). Table II shows unit prices.
Resource Volumes
Using means, standard deviations and min-max values for
continuous data, and proportions for dichotomous data, we
generated annual resource volumes of treatment planning and
delivery times.
Costs
To capture all costs, i.e., those of the equipment plus those
related to its administration and maintenance, and other costs
related to clinical assessment, treatment planning, delivery
and follow up, we included cost items as machine, installa-
tion, warranty, physician fees, salaries of nurses, therapists
and physicists. We did not include costs related to PSA test-
ing, tumor recurrence, loss of productivity from hospitaliza-
tion, disability or death, and patients’ out-of-pocket expenses.
Finally, we multiplied the unit prices of cost items with
resource volumes to compute the total costs for all groups.
Outcomes
The main outcomes were cost per patient, cost per cure
and cost per QALY related to each regimen and each sys-
tem. We defined cure as no biochemical evidence of disease
(bNED) at 5 years. Using Fowler’s model (4), we computed
bNED for each regimen. We computed QALYs assuming a
life expectancy of 20 years, utility of 0.8 post-radiation and
utility of 0.68 post-recurrence (14). As there are no data to
suggest that one modality is better than the other in terms of
toxicity, we did not include any adverse events.
Analysis
First, we calculated cost per patient, cost per cure and cost
per QALY for all groups. Next, we subtracted respective
outcomes of each group from the reference standard. This
yielded the incremental cost/patient, incremental cost/cure
and incremental cost/QALY for each system and regimen.
We discounted future costs at 5% rate to the present dollar
value.
There was some uncertainty in our estimates of daily hours
of operation for the robotic system and in-room treatment
times. This is partly because these parameters are depen-
dent upon volumes of patients – large volume of stereotactic
cases would increase the daily hours of operation of the
robotic system – large number of prostate SBRT cases
would enhance efficiency which in turn would reduce in-
room treatment times. To account for these uncertainties, we
performed sensitivity analyses. We varied daily hours from
2 hours (low volume setting) to 10 hours (high volume set-
ting), and we recalculated cost per patient for the robotic
system. Similarly, we varied in-room treatment times from
40 to 50 minutes for robotic, 15 to 30 minutes for arc-based,
and 25 to 35 minutes for fixed-gantry systems, and we re-
calculated cost per patient for each system. In addition, we
performed a probabilistic analysis by using Monte Carlo
simulation on parameters of in-room treatment times, daily
hours of operation, cure rate and life expectancy and com-
puted 95% intervals of the incremental cost/patient. We also
graphically compared arc-based and fixed-gantry systems on
cost per patient, cost per cure and cost per QALY stratified
by regimens.

Technology in Cancer Research & Treatment 2014 April 16. Epub ahead of print
176
For budget impact of acquiring the robotic system, we took
the difference of annual cost of acquiring the unit (purchase
and installment) and its maintenance, between robotic and
arc-based or fixed-gantry systems. We assumed a variation
of 5% in purchase price, and up to 15% increment in repair
costs depending upon utilization.
We reported costs in Canadian dollars (1 Canadian
dollar 5 1.01 US dollar; Dec 2012).
Results
When all regimens and delivery systems were compared cost
for SBRT varied from $4368/patient (arc-based) to $6333/
patient (robotic), cost for 12 fraction varied from $4489/
patient (arc-based) to $5664/patient (fixed-gantry), cost
for 20 fraction varied from $4956/patient (arc-based) to
$6462/patient (fixed-gantry) and cost for standard ­regimen
varied from $5935/patient (arc-based) to $7992/patient
Figure 3: Cost effectiveness analyses. (A) shows cost/patient of robotic (checker) compared to arc-based (light grey) and fixed-gantry (grey) systems.
(B) and (C) show cost/cure and cost/quality adjusted life years. Cure was defined as 5 years biochemical relapse free survival.
Technology in Cancer Research & Treatment 2014 April 16. Epub ahead of print
Sharieff et al.
(fixed-gantry). Similar pattern was observed for cost per cure
and cost per QALY (Figure 3). Probabilistic analysis favored
arc-based system over other systems for all regimens (data
not shown).
When SBRT regimen using robotic system was compared to
the standard regimen using fixed-gantry system, the incre-
mental cost per patient was $-1658 (95% interval: $-1880,
$-414), incremental cost per cure was $-12,532 ($-14,283,
$-3135), and incremental cost per QALY was $-2497
($-2846, $-622).
In setting of low volume (2 hours of daily operation), cost
of robotic SBRT was $9363/patient and in setting of high
volume (10 hours of daily operation), it was $5263/patient.
When in-room time for SBRT was varied, cost of robotic sys-
tem ranged from $5892/patient to $6523/patient, cost of arc-
based system ranged from $3888/patient to $4453/patient,
Economics of Prostate Radiotherapy
and cost of fixed-gantry system ranged from $4076/patient
to $4642/patient.
The budget impact was $151,776/year (95% interval:
$144,478/year, $159,947/year) for acquiring the robotic sys-
tem rather than an arc-based system or a fixed-gantry system.
Discussion
We evaluated the cost implications of implementing hypo-
fractionated regimens for the treatment of prostate cancer
through robotic, arc-based and fixed-gantry-based systems.
When total investment costs were considered, we found
robotic system to be more costly than arc-based and fixed-
gantry systems. When robotic SBRT was compared to the
standard (39 fraction) regimen, the cost of robotic SBRT
($6333/patient) was comparable to the cost of standard
regimen which varied from $5935/patient for arc-based to
$7992/patient for fixed-gantry. However, when cost per cure
and cost per QALY are considered, due to the higher bNED
rates, robotic SBRT appears more cost effective than the
standard arc-based and fixed-gantry systems. Nonetheless,
if arc-based and fixed-gantry systems are used for SBRT,
these systems could deliver treatment at lower costs than
the robotic system. To date, published bNED data on
prostate SBRT are limited to the use of robotic system
(8, 9). Emerging data on other delivery systems appear
promising (11, 15).
There is limited literature on the cost effectiveness of radia-
tion therapy for prostate cancer. Using SEER-Medicare data
from 2002 to 2005, Nguyen and colleagues estimated that
cost of standard fraction intensity modulated radiotherapy
(IMRT) in the US ranged from $31,575 to $37,125 (16).
They included all risk categories of prostate cancer patients
and included inpatient and outpatient health expenditures
accrued up to 12 months prior to the diagnosis of prostate
cancer. In another US study, Parthan and colleagues com-
pared cost effectiveness of SBRT with IMRT and proton
therapy for localized prostate cancer from a societal per-
spective (17). Based on Medicare rates and published litera-
ture, they estimated the costs at $20,889 (SBRT), $28,805
(IMRT) and $65,250 (proton therapy); they did not provide
a breakdown of costs. We limited our cost analysis to low
risk prostate cancer patients from the time of referral to a
radiation oncologist from a payer’s perspective. Thus, our
estimates of SBRT cost ($6333) and IMRT cost ($7992/
patient) are relatively low. We have described the cost
items and resource volumes so that by using local unit
prices, decision makers could generate cost estimates in
their own settings.
Our results should be used in the context of study limita-
tions. We performed costing from payer’s perspective. Thus,
Technology in Cancer Research & Treatment 2014 April 16. Epub ahead of print
177
potential cost savings from a hypofractionated regimen
related to patients’ out of pocket expenses such as commut-
ing, parking and loss of productivity were not captured. In
addition, our cost utility analysis had limitations due to lack
of data on quality of life. As long term data from ongoing
studies become available, further analyses can be carried out
to capture this important dimension. Nevertheless, we carried
out probabilistic analyses to account for the uncertainty in
parameter estimates.
Conclusions
In settings of moderate to high volume (6-10 hours of daily
operation), SBRT with the robotic system is cost effective
compared to the standard regimen. If SBRT can be delivered
with equivalent efficacy, the arc-based system would be the
most cost effective system; to-date published literature on
prostate SBRT is limited to robotic system. Given that the
robotic system has higher budget impact than arc-based and
fixed-gantry systems, decision-makers need to judge whether
there is enough patient volume in their own setting to justify
the purchase of the robotic system.
Conflict of Interest
None declared.
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Received: October 5, 2013; Revised: January 11, 2014;
Accepted: January 15, 2014