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RaySearch White Paper Biological optimization using the equivalent uniform dose (EUD) in Pinnacle

3
.

WP-EUD rev. 1, 0310
Pinnacle
3
and P
3
IMRT are registered trademarks of Philips Medical Systems. NPSOL

is a registered Trademark of Stanford University

Biological optimization using the equivalent
uniform dose (EUD) in Pinnacle
3
.

RaySearch Laboratories AB, Stockholm Sweden

Introduction
The foundation of any optimization process is the
definition of the objectives and/or constraints. For
inverse planning of radiotherapy, the objectives and
constraints should drive the optimization to create a
plan with a beneficial dose distribution in the patient.
Since a dose distribution is a large three-dimensional
field, it is hard to even present all data in a readable
form, and nearly impossible to find a single value
that captures all desired features in the distribution.
One common way of presenting a dose distribution
is by using dose volume histograms (DVH). In most
treatment planning systems, these diagrams are also
the bases for the objective functions when optimizing
IMRT. As efficient the DVHs may be as an evalua-
tion tool, they may not be the best candidates for cre-
ating objective functions.
The equivalent uniform dose
Consider a region of interest (ROI) in a patient. De-
pending on the dose delivered to that region, there
will be different biological effects. Assuming that the
biological effects can be quantified on some one-
dimensional scale, for example the level of functional
reduction, the risk for some complication, or the
grade of tumor control, there will be countless dose
distributions that give the same biological effect.
The idea behind the equivalent uniform dose is to,
for a given non-uniform dose distribution, find the
uniform dose that gives the same biological effect.
The dose level of that uniform dose is then the
equivalent uniform dose of the non-uniform distri-
bution.
Niemerko [1] has suggested that the EUD could be
defined as

a N
i
a
i
d
N
EUD
1
1
1
|
|
.
|

\
|
=

=
,
where
i
d is the dose in voxel i , N is the number of
voxels in the ROI, and a is called the volume pa-
rameter, which will be described further below.
In P
3
IMRT the equation is slightly modified to allow
voxels to be only partially included in a region of in-
terest. With
i
v denoting the fraction of the ROI that
is occupied by voxel i , the EUD is calculated as

a N
i
a
i i
d v EUD
1
1
|
|
.
|

\
|
=

=
.
The volume parameter, a
The EUD model is parameterized by one biological
parameter, a . The parameter should be chosen so
that the EUD reflects the intended biological proper-
ties. The choice of a has the following effect on the
EUD value
Effect Suitable organs
1 < a
Lower doses are given
higher weight, so that
cold spots affect the
EUD to a large extent.
Targets.
1 = a
This corresponds to the
mean dose. Cold and
hot spots are given
equal weight.
Parallel organized
normal tissue,
such as lung and
liver.
1 > a
Larger doses are given
higher weight, so that
hot spots affect the
EUD to a large extent
Serial tissue, such
as the spinal cord.
Parameter a may be determined empirically by fit-
ting with dose-volume data. As an alternative, a can
be treated as a freely adjustable parameter whose
value is determined by trial-and-error to achieve the
best dose distributions, which is the ultimate goal.

RaySearch White Paper Biological optimization using the equivalent uniform dose (EUD) in Pinnacle
3
.

WP-EUD rev. 1, 0310
Pinnacle
3
and P
3
IMRT are registered trademarks of Philips Medical Systems. NPSOL

is a registered Trademark of Stanford University

Objectives and constraints
In order to optimize based on EUD, objective func-
tions have to be formulated. In the P
3
IMRT opti-
mized module, ORBIT [2], the EUD-based objective
function are defined as P
3
IMRT

2
0
0
0
) , ( ) (
|
|
.
|

\
|
=
EUD
EUD EUD
EUD EUD EUD F ,
where
0
EUD is a dose level specified by the user, and

( )
( ) EUD min for
EUD for target
EUD max for
1 ) , (
0
0
0

=
EUD EUD H
EUD EUD H
EUD EUD ,
where ( ) H is the Heaviside step function. The max
and min EUD objective function have the obvious
interpretations of penalizing too high or too low
EUD values respectively. Target EUD means that any
deviation from the given
0
EUD will be penalized, so
the optimizer will try to achieve exactly that value.
The logical choice of objective functions for a critical
structure is therefore a maximum EUD objec-
tive/constraint with 1 a . The higher the value of a ,
the more effort will be given to avoiding hot spots.
For targets, the logical choice would be a minimum
or target EUD objective/constraint with 1 < a . The
lower the value of a , the more effort will be given to
avoiding cold spots.
References
[1] Niemierko A. A generalized concept of equivalent
uniform dose (EUD). Med. Phys. 26(6):1101, 1999.
[2] J. Lf, Development of a general framework for
optimization of radiation therapy, Stockholm Uni-
versity, 2000.

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