INTERNATIONAL

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IN OPERATIONAL
Intl. Trans. in Op. Res 22 (2015) 635645 RESEARCH
DOI: 10.1111/itor.12093

A fast beam orientation optimization method that enforces

geometric constraints in IMRT for total marrow irradiation
Chieh-Hsiu Jason Leea , Dionne M. Alemana and Michael B. Sharpeb
a
Department of Mechanical and Industrial Engineering, University of Toronto, 5 Kings College Road, Toronto,
ON M5S 3G8, Canada
b
Department of Radiation Oncology, Princess Margaret Cancer Centre, Radiation Medicine Program, University of
Toronto, 610 University of Avenue, Toronto, ON M5G 2M9, Canada
E-mail: chjlee@mie.utoronto.ca [Lee]; aleman@mie.utoronto.ca [Aleman]; michael.sharpe@rmp.uhn.on.ca [Sharpe]
Received 20 March 2013; received in revised form 2 March 2014; accepted 13 March 2014

Abstract
The beam orientation optimization (BOO) problem for intensity-modulated radiation therapy (IMRT) is the
selection of beams for radiation delivery. Conventionally, it is desirable for beams to be spatially separated to
ensure a homogeneous dose. However, many BOO approaches yield clustered beams. This issue is especially
prevalent for total marrow irradiation (TMI), where the target is very large and spread throughout the
patients body. Based on previous set-cover formulations of the BOO problem for TMI-IMRT, we propose
an extension that enforces geometric beam constraints by iteratively removing beams violating geometric
constraints within the set-cover framework. After beams are selected, they are used as input to a fluence map
optimization solver to obtain optimal fluence maps. Results for a clinical TMI case meet clinical guidelines
for target coverage and differentiation of organ and target doses.

Keywords: health services; set cover; optimization; heuristics; integer programming; medicine

1. Introduction

Total marrow irradiation (TMI) is frequently used as a precursor to a bone marrow transplant.
In TMI, radiation is delivered to the patients existing disease bone marrow so that the newly
transplanted stem cells can propagate. Because the treatment area in TMI (the entire skeleton) is
large, TMI is typically delivered by positioning the patient on the floor and then irradiating the
patient with two uniform beams of radiation. The patient is then rotated and irradiated from the
other side. This method achieves adequate target coverage, but even with lead shields are provided
to protect some organs at risk (OARs), it is possible that TMI accuracy could be improved using
intensity modulated radiation therapy (IMRT).


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In traditional clinical settings, TMI is performed with the patient about 2 m from the radiation
source because the size of beam increases with distance from the source, and thus patient can be
treated with just two beams. However, at such large distances, the accuracy of the treatment cannot
be guaranteed. In order to deliver an IMRT plan using TMI, the patient must first be positioned
at isocenter (about 100 cm from the radiation source), which means that two beams are no longer
sufficient to cover the patients body. Several beams must be used, and the process of selecting these
beams is called beam orientation optimization (BOO). Typically, BOO is performed, and then the
resulting beams are used as input to a fluence map optimization (FMO) model that determines the
optimal fluence maps for each beam.
We specifically investigate fast BOO methods for TMI that enforce geometric beam constraints,
that is, constraints requiring a minimum amount of space between beams. Beam clustering (multiple
beams positioned in a close proximity) is clinically undesirable as such a situation prevents an
effective spreading of the dose around the patient, which helps to lower the amount of radiation
dose delivered to healthy structures. Thus, geometric constraints may be an important consideration,
especially given potential patient positioning uncertainties.
Despite the many previous studies in BOO, clinical TMI treatments do not attempt to optimize
beam locations due to (a) the computational difficulty in performing BOO on a treatment area that
is generally 100 times larger than a head-and-neck treatment, and (b) the difficulty in setting up the
patient in a way consistent with the patient images used in planning the treatment. We address the
first problem in this paper, and emphasize spacing the beams around a fixed patient (i.e., we do not
consider repositioning the patient) to mitigate patient positioning difficulties in the second problem.
Previous BOO studies for IMRT have mostly emphasized coplanar beam selection (e.g., Acosta
et al., 2008; Aleman et al., 2008; Bangert and Oelfke, 2010; Bertsimas et al., 2013; Cao et al.,
2012; Craft, 2007; Ehrgott and Johnston, 2003; Lee et al., 2006; Lim and Cao, 2012; Lim et al.,
2008; Pugachev and Xing, 2002). Coplanar beams are those beams arising from gantry rotation
only. Noncoplanar beams, which incorporate couch movement in addition to gantry rotation, are
necessary for TMI to irradiate the large treatment area, but have been less studied (e.g., Aleman
et al., 2009; Das and Marks, 1997; Lee et al., 2003; Meedt et al., 2003; Misic et al., 2010; Wang et al.,
2005). Common techniques used to solve the noncoplanar BOO problem include neighborhood
search methods (Cao et al., 2012; Das et al., 2003; Meedt et al., 2003; Misic et al., 2010) (even
applied to TMI; Misic et al., 2010), but these methods are computationally slow, requiring hours
to run. Mixed integer programming approaches that simultaneously solve the BOO and FMO
problems have been presented for coplanar (Lee et al., 2006; Lim and Cao, 2012) and noncoplanar
beams (Lee et al., 2003), but such approaches are inappropriate for TMI as the increased problem
sizespecifically, the much larger number of beams and voxels (cubes of patient tissue)renders
mixed integer optimization intractable. Nonlinear programming formulations of BOO (Bertsimas
et al., 2013) are also computationally challenging for TMI.
Set-covering formulations applied to BOO (Acosta et al., 2008; Ehrgott et al., 2008; Lee et al.,
2011) are promising due to their transparent ability to incorporate noncoplanar beams. The set-
cover problem (SCP) approaches in Acosta et al. (2008) and Ehrgott et al. (2008) appear to only
consider coplanar beams, and were applied to head-and-neck cases with a user-specified number of
beams to select. The SCP problems were solved via integer programming, which is likely to be slow
for TMI. The heuristic-based SCP approach in Lee et al. (2011), on the other hand, was successfully


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applied to TMI. This method does not require a user-specified number of beams, runs in seconds,
and achieves clinically acceptable treatments. We therefore build on the SCP method in Lee et al.
(2011) to incorporate geometric beam constraints.
Although good treatments were obtained in Lee et al. (2011), one property of the solutions was
a tendency toward spatial clustering of the beams. Beam selection with consideration of geometric
beam constraints has been studied with a goal to obtain maximum beam separation (Das and
Marks, 1997), with predetermined beam configuration templates (Sailer et al., 1994), and with
minimum beam separation requirements (Das et al., 2003; Meyer et al., 2005). The minimum beam
separation approach is attractive for TMI since predetermined beam configurations and maximum
separation requirements may be too restrictive, and we have experimentally observed that the beam
solution has a bigger impact on the quality of final treatment plan in TMI than in site-specific
treatments, for example, head-and-neck and prostate. The minimum beam separation approach of
Das et al. (2003) relies on EUD (equivalent uniform dose), which is too computationally expensive
for TMI given that simply calculating dose from all beams to all voxels in TMI takes minutes,
and EUD requires dose calculations in every iteration. Similarly, the minimum beam separation
approach of Meyer et al. (2005) requires distance calculations between structures and beams that
are also computationally expensive for TMI.
We therefore devise a new approach based on SCP to reduce beam clustering in BOO through
iterative geometric constraint enforcement, with an emphasis on computation speed. We modify the
original SCP algorithm in Lee et al. (2011) (herein referred to as original SCP) to disallow beams
that are inappropriately close to previously selected beams. The rest of this paper is organized as
follows. Section 2 presents the SCP formulation of the BOO problem and describes SCP heuristic
modifications to enforce geometric constraints. Section 3 provides computational and clinical results
on a TMI case, as well as comparisons of the heuristic solutions to solutions obtained from an integer
programming model. Section 4 contains conclusions and future work.

2. Methods and materials

The BOO problem is formulated as an SCP (Acosta et al., 2008; Ehrgott et al., 2008; Lee et al., 2011)
as follows. In an SCP formulation, the goal is to cover (irradiate) all target voxels V using some
or all of the beams in candidate beam set C . Each beam irradiates a set of target voxels, and goal
is to find the best set of beams that covers the target voxels (according to some scoring metric for
each beam). In the case where all beams have the same score, the problem is to select the minimum
number of beams to cover the target voxels.
Let xi {0, 1}, i C represent whether or not the ith beam in C is selected. Also let ai j {0, 1}
indicate whether beam i irradiates voxel j V . The matrix of values A = {ai j } is called the adjacency
matrix. In order for a beam to hit a voxel, that is, ai j = 1, we require that the amount of dose
delivered by beam i to voxel j per unit radiation intensity be larger than . To ensure adequate
target coverage, each voxel must be covered k times, where k 1; this set-cover variation is called a
k-cover.
Each beam i C has a set of neighboring beams N (i) that fall within geometric limits that must
be constrained; if beam i is selected, then none of its neighbors in N (i) can be selected. Letting


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functions gantry() and z() represent a beams gantry angle and couch position in the z dimension,
respectively, we define the neighborhood as
 
N (i) =  C : (gantry(i) gantry()) mod 360 g |z(i) z()| z .
The values g and z represent the minimum allowable separation between beams in gantry angle and
couch-z position, respectively. The modulus operator on the gantry angle separation is to account
for the cyclical nature of gantry angles, for example, 350 = 10 . Note that a beam is included in
its own neighborhood.
Assuming a cost for each beam (ci ), the BOO-SCP problem with geometric constraints is then

minimize ci xi (BOO-SCP-Geo)
iC

subject to ai j xi k jV (1)
iC

x 1 iC (2)
N (i)

xi {0, 1} i C. (3)
In the model, the objective is to minimize the total cost of the solution, where lower cost indicates
higher quality beams. Constraint 1 uses the adjacency matrix to require that every voxel j V is
covered at least k times by the selected beams, and constraint 3 prevents geometric clustering by
ensuring that at most one beam can be selected from each possible neighborhood, defined as N (i)
for each beam i C . For example, if beam k is selected for use in the treatment plan (xk = 1), then
all beams  N (k) are precluded (i.e., x = 0 for all beams  N (k)).
The following sections detail two heuristic methods to obtain fast solutions to the BOO-SCP-
Geo problem. Each approach reduces the set of candidate beams either prior to or during the beam
selection process. After selecting beams, the FMO method described in Misic et al. (2010) is used
to obtain the final treatment plans.

2.1. Set-cover with geometric constraints

We modify the original SCP algorithm (Lee et al., 2011) to consider geometric constraints iteratively.
We refer to this approach as Geo-SCP (Algorithm 1). As in Lee et al. (2011), we consider an initial
candidate set of beams obtained by gantry rotation and couch translation in the z dimension. In
each iteration, once a beam i has been selected from C and added to the set of solution beams B , the
voxels that newly reach k-cover (C ) are removed from the set of voxels V . Then, neighboring beams
of i that violate geometric spacing constraints (N (i )) are removed from the candidate beam pool
C . The reduced set of candidate beams is used in the subsequent iteration, and the action of selecting
the best scoring beam and removing its neighbors is repeated in each iteration. This heuristic runs
until k-cover is achieved for all voxels, or until the percentage improvement in the number of newly
covered voxels decreases below some threshold .

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Algorithm 1. Geo-SCP: SCP heuristic with geometric constraints

Require: C set of all candidate beams, V set of all voxels, A adjacency matrix, k cover level,
stopping criteria
1: B , solution set of beams
2: V V, set of newly k-covered voxels
3: cover( j) = 0, j V, current cover level of voxels
4: while |V| 0 AND |V |/|V| do
5: ci 1Chvatal scoring, i C
6: i = arg miniC {ci }
7: B B i
8: C C N (i )
9: V
10: for j V AND ai j = 1 do
11: cover( j) cover( j) + 1
12: if cover( j) = k then
13: V V j
14: end if
15: end for
16: V V V
17: end while
18: return B

In scoring beams, we use the Chvatal scoring (Chvatal, 1979) shown to be most effective for
set-cover formulations of BOO compared to other beam scoring metrics (Lee et al., 2011). As
shown in step 5, the scores in the Chvatal method must be recalculated in each iteration. Contrary
to the generalized BOO-SCP-Geo minimization model, the Chvatal scoring assigns higher scores
to preferable beams, so a beams score is the negative of the Chvatal score.

3. Results

We apply our BOO methods to a clinical TMI case provided by Princess Margaret Cancer Cen-
tre (PMCC), Toronto, ON, Canada, under ethical clearance. SCP methods were implemented
in MATLAB. Gurobi Optimizer 4.0 was used to solve the IP models. We consider 396 can-
didate beams, obtained from gantry angles 0 350 in 10 increments, and 11 couch posi-
tions spaced 10 cm apart. We enforce a minimum 20-cm couch separation on the z-axis be-
tween the same gantry angles, and examine minimum gantry angle separation of 20 60 in 10
increments.
As shown in Table 1, the PTV (planning tumor volume, the targeted bone marrow) contains
331,715 voxels that must be covered. From the 396 beams considered in the original candidate beam
set, there are 17593146 beamlets per beam that can reach the target, with a mean of 2469 beamlets
per beam. The number of beamlets per beam is much larger than in site-specific treatments due
to the fact that the target is essentially the entire skeleton, so each beam contains thousands of
usable beamlets. Creation of the adjacency matrix for all 396 beams requires approximately five
minutes.

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Table 1
Number of voxels in each structure

Structure No. of voxels

Left lung 29,274
Right lung 40,248
Spinal cord 1856
Heart 18,746
Left kidney 5638
Right kidney 5263
Liver 74,986
Stomach 12,195
PTV 331,715
Parotid and submandibular glands 959
Esophagus 1138
Bowel 119,557
Bladder 4662
Oral cavity 4926
Left eye 130
Right eye 117
Total 651,410
The bone marrow is the planning target volume (PTV).

Clinical guidelines for TMI are that at least 95% of the target voxels receive at least 12 Gy
(D95 12 Gy), while no voxels can receive more than 30 Gy to prevent fibrosis. Unfortunately, there
are no clinical guidelines to indicate acceptable OAR doses in TMI settings. This lack of information
is likely due to the current manner in which TMI is delivered clinically, in that the inability to deliver
accurately conformed dose forces clinicians to be primarily concerned with target coverage at the
expense of OARs; lead shields placed over some organs (e.g., kidneys) are sometimes used clinically
to mitigate OAR dose.
To evaluate the treatment quality, we examine the dose volume histograms (DVHs) that present
the amount of dose delivered into a volume of a structure. As exact organ sparing criteria for TMI is
unknown, we simply seek plans that have significant separation of the target and organ DVH curves.
For comparison, Fig. 1 illustrates the treatment plans obtained using a 5-cover SCP formulation
with no geometric constraints. As the figure shows, clustering of beam orientations is significant.

3.1. Optimal integer programming

As shown in Table 2, although the heuristics were allowed to not achieve a full k-cover for all voxels,
the rigidity of the BOO-SCP-Geo IP formulation resulted in infeasibility for the 5-cover for nearly
all gantry separations except the most lenient, 20 . This one feasible solution was also the only IP
solution to achieve the clinical requirement D95 12 Gy, and also yielded the best FMO objective
function value. In order to have feasibility for all test gantry separations, at most a 3-cover could
be enforced, however, Fig. 2 illustrates that the dose delivered to OARs suffered in those solutions
with only 12 beams, as found by all the 3-cover implementations.

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Plot of beam origins
100 24 beams
hemiPTV
90 lt lung
rt lung
80 cord
Heart
70 Anterior

Percent volume (%)

Kidney_L
Kidney_R
60
Liver
50 stomach
parotids and smg
40 esophagus
bowel
30 Bladder
oral cavity Posterior 160
20 Eye_L RHS 140
120
Eye_R 100
10 Spine 80
60
40
0 20
0 5 10 15 20 25 30 35 40 Patient lateral LHS 0 Couch
Dose (Gy)

Fig. 1. DVHs and beam orientations using a 5-cover SCP approach with no geometric constraints, resulting in 24 beams
grouped in clusters. The patients head is located at a couch position of approximately 160 cm.

Table 2
Number of beams, computation times, and D95 values for the IP approach

k-cover
3 4 5
Minimum Solution FMO Solution FMO Solution FMO
gantry No. of time D95 objective No. of time D95 objective No. of time D95 objective
separation beams (seconds) (Gy) function beams (seconds) (Gy) function beams (seconds) (Gy) function
20 12 274 11.3 16,424 16 256 11.3 14,920 22 250 12.0 13,039
30 12 276 11.6 14,622 17 270 11.6 14,745
40 12 300 11.7 14,038 19 205 11.3 15,913
50 12 260 11.6 15,674
60 12 285 11.9 14,934
Bold values indicate treatments that satisfy the D95 12 Gy requirement.

Despite the clinical shortcomings of the IP approach and feasibility issues, Gurobi Optimizer
4.0 was able to solve the IP problems with feasible solutions quickly, requiring no more than
five minutes, excluding the five minutes necessary to generate the adjacency matrix. Interestingly,
the FMO objective function values for the feasible 3- and 4-cover scenarios were < 1% different
on average, while the 5-cover showed an average 13.9% improvement over the 3- and 4-cover
scenarios.

3.2. Set-cover with geometric constraints

According to the findings in Lee et al. (2011), we use  = 0.1, = 0.02, and a multi-cover of
k = 5. Computation times and resultant D95 values for the Geo-SCP approach are presented in
Table 3. As the table shows, each of the treatment plans obtained using Geo-SCP meets clin-
ical target coverage guidelines, and the percentage of voxels not covered is less than = 0.02
stopping criteria. The DVHs and beam positions for the 20 - and 60 -separation implementa-
tions with 20 cm couch separation are shown in Fig. 3. The DVHs show clinically acceptable

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100 100
hemiPTV hemiPTV
90 lt lung 90 lt lung
rt lung rt lung
80 cord 80 cord
Heart Heart
70 70

Percent volume (%)

Kidney_L Kidney_L

Percent volume (%)

Kidney_R Kidney_R
60 60
Liver Liver
50 stomach 50 stomach
parotids and smg parotids and smg
40 esophagus 40 esophagus
bowel bowel
30 Bladder 30 Bladder
oral cavity oral cavity
20 Eye_L 20 Eye_L
Eye_R Eye_R
10 10

0 0
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Dose (Gy) Dose (Gy)
Plot of beam origins Plot of beam origins
22 beams 12 beams

Anterior Anterior

Posterior 160 Posterior 160

140 RHS 140
RHS 120 120
100 100
80 80
Spine Spine 60
60
40 40
20 20
LHS 0 Couch LHS 0 Couch
Patient lateral Patient lateral

Fig. 2. DVHs and beam orientations using the IP approach. The patients head is located at a couch position of
approximately 160 cm. Left: minimum 20 gantry separation with 5-cover constraint, resulting in 22 beams. Right:
minimum 60 gantry separation with 3-cover constraint, resulting in 12 beams.

Table 3
Computational and target coverage results using Geo-SCP

Minimum gantry No. of solution SCP FMO D95 Percentage of voxels FMO
separation beams time (seconds) time (minutes) (Gy) not k-covered objective function
20 24 16 192 12.5 1.41 11,452
30 34 20 327 12.6 0.53 10,877
40 36 20 161 12.6 0.69 10,894
50 35 19 188 12.4 0.90 11,104
60 34 18 119 12.1 0.95 12,022

separation of the PTV and OARs, while the resulting beam positions for both 20 and 60 gantry
separation clearly avoid the clustering seen in the original SCP (Lee et al., 2011). Interestingly,
the 60 gantry separation scenario requires significantly more beams to treat the patient (35
beams compared to 24). Computationally, the SCP algorithm required < 20 seconds to run de-
spite having to rescore and remove several beams from the candidate set in each iteration. In
terms of FMO objective function value, Geo-SCP improved on the best IP solution by 15.7% on
average.

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100 100
hemiPTV hemiPTV
90 lt lung 90 lt lung
rt lung rt lung
80 cord 80 cord
Heart Heart
70 70

Percent volume (%)

Percent volume (%)

Kidney_L Kidney_L
Kidney_R Kidney_R
60 60
Liver Liver
50 stomach 50 stomach
parotids and smg parotids and smg
40 esophagus 40 esophagus
bowel bowel
30 Bladder 30 Bladder
oral cavity oral cavity
20 Eye_L 20 Eye_L
Eye_R Eye_R
10 10

0 0
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Dose (Gy) Dose (Gy)

Plot of beam origins Plot of beam origins

24 beams 35 beams

Anterior Anterior

Posterior 160 Posterior 160

RHS 140 RHS 140
120 120
100 100
80 Spine 80
Spine 60 60
40 40
20 20
Patient lateral LHS 0 Couch Patient lateral LHS 0 Couch

Fig. 3. DVHs and beam orientations using the Geo-SCP approach. The patients head is located at a couch position of
approximately 160 cm. Left: minimum 20 gantry separation and 20 cm couch separation, resulting in 24 beams;
Right: minimum 60 gantry separation and 20 cm couch separation, resulting in 35 beams.

4. Conclusions and future work

We present a fast approach to solving the BOO problem while considering geometric constraints,
thereby eliminating beam clustering present in previous TMI studies. The resulting treatment plans
and FMO objective function values demonstrate that the Geo-SCP method is efficient in select-
ing beams, and consistently obtains high-quality TMI treatments where the target received clin-
ically satisfactory dose, and the OAR dose was significantly differentiated from the target dose.
The methods were compared to the optimal integer programming solutions, but pure IP models
were unable to reliably find feasible solutions for a 5-cover, and the small number of beams found for
the 3-cover resulted in poor treatment plan quality and FMO objective function values. Although
the IP solutions required only five minutes to run, the Geo-SCP heuristic was faster, needing no
more than 20 seconds.
Given the nature of geometric restrictions on the beam orientation set, a constraint program-
ming approach to identify feasible candidate beam sets a priori could yield reduced computation
time by allowing for the use of a simple SCP heuristic (e.g., Chvatal scoring; Chvatal, 1979) in-
stead of Geo-SCP. By identifying feasible sets in advance, rather than iteratively, such an approach
might result in higher quality beam sets being selected. Future investigations will therefore ex-
amine the development of a constraint programming framework to enforce geometric constraints
in BOO.

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Acknowledgments

This work was funded by the Natural Sciences and Engineering Research Council Discovery Grant
program and The Canada Foundation for Innovations Leaders Opportunity Fund.

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