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A Large-Scale Combinatorial Many-Objective Evolutionary Algorithm for

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IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR
A Large-Scale Combinatorial Many-Objective
Evolutionary Algorithm for Intensity-
Modulated Radiotherapy Planning
Ye Tian, Yuandong Feng, Chao Wang, Ruifen Cao, Xingyi Zhang, Senior Member, IEEE
Xi Pei, Kay Chen Tan, Fellow, IEEE, and Yaochu Jin, Fellow, IEEE
Abstract—Intensity-modulated radiotherapy (IMRT) is
one of the most popular techniques for cancer treatment.
However, existing IMRT planning methods can only generate
one solution at a time, and consequently medical physicists
should perform the planning process many times to obtain
diverse solutions to meet the requirement of a clinical
case. Meanwhile, multi-objective evolutionary algorithms
(MOEAs) have not been fully exploited in IMRT planning
since they are ineffective in optimizing the large number
of discrete variables of IMRT. To bridge the gap, this paper
formulates IMRT planning into a large-scale combinatorial
many-objective optimization problem, and proposes a co-
evolutionary algorithm to solve it. In contrast to existing
MOEAs handling high-dimensional search spaces via vari-
able grouping or dimensionality reduction, the proposed
algorithm evolves one population with fine encoding for
local exploitation and evolves another population with rough
encoding for global exploration. Moreover, the convergence
speed is further accelerated by two customized local search
strategies. The experimental results verify that, the proposed
algorithm outperforms state-of-the-art MOEAs and IMRT
planning methods on a variety of clinical cases.
Index Terms—Intensity-modulated radiotherapy, large-
scale optimization, many-objective optimization, combina-
torial optimization, evolutionary computation
Manuscript received –. This work was supported in part by the
National Key R&D Program of China under Grant 2018AAA0100100,
in part by the National Natural Science Foundation of China under
Grant 61822301, Grant 61876123, Grant 61906001, Grant 62106002, and
Grant 62136008, in part by the Collaborative Innovation Program
of Universities in Anhui Province under Grant GXXT-2020-013 and
Grant GXXT-2020-051, in part by the Research Grants Council of
the Hong Kong Special Administrative Region, China under Grant
PolyU11202418 and Grant PolyU11209219, and in part by an Alexander
von Humboldt Professorship for Artificial Intelligence funded by the
Federal Ministry of Education and Research, Germany. (Corresponding
author: Xingyi Zhang.)
Y. Tian, C. Wang, R. Cao, and X. Zhang are with the Information
Materials and Intelligent Sensing Laboratory of Anhui Province, An-
hui University, Hefei 230601, China (email: field910921@gmail.com;
wangchao8@ahu.edu.cn; rfcao@ahu.edu.cn; xyzhanghust@gmail.com).
Y. Feng is with the School of Computer Science and Tech-
nology, Anhui University, Hefei 230601, China (email: yuan-
dongfeng@stu.ahu.edu.cn).
X. Pei is with the School of Nuclear Science and Technology, Univer-
sity of Science and Technology of China, Hefei 230026, China (email:
xpei@ustc.edu.cn).
K. C. Tan is with the Department of Computing, The Hong Kong
Polytechnic University, Hong Kong SAR (email: kctan@polyu.edu.hk).
Y. Jin is with the Faculty of Technology, Bielefeld University, Bielefeld
33619, Germany (email: yaochu.jin@uni-bielefeld.de).
0000–0000/00$00.00 ⃝
c 0000 IEEE
1
I. I NTRODUCTION
I NTENSITY-modulated radiotherapy (IMRT) is cur-
rently one of the most mature and widely used tech-
niques for cancer treatment. According to the clinical re-
quirement of a cancer case, IMRT can provide acceptable
treatment plans based on multiple radiation beams with
different shapes and intensities [1]. As plotted in Fig. 1, a
linear accelerator can produce multiple beams by acceler-
ating electrons onto a target, where the emitted photons
are transmitted through a multileaf collimator (MLC)
and form a therapeutic field [2]. The core issue in IMRT
planning is to obtain a therapeutic field by adjusting the
weights of beams and the positions of MLC leaves, so as
to maximize the tumor control probability and minimize
the normal tissue complication probability [3].
The optimization of beam weights and MLC leaf
positions is essentially a complex optimization problem,
which contains many conflicting objectives and a large
number of discrete variables (e.g., the test instances
solved in Section IV contain five objectives and up to
3050 variables). This gained much research attention in
the last three decades, where a number of planning
methods based on various optimizers have been tailored.
Earlier IMRT planning methods are mostly based on
two-step optimization, where the fluence map optimiza-
tion and the MLC sequencing are conducted in two
steps. The fluence map optimization aims to obtain the
optimal beam weight of each grid in the discretized
field, which is achieved by analytical algorithms (e.g.,
Fourier transform [4] and Taylor series expansion [5]),
mathematical programming methods (e.g., quadratic
programming [6] and conjugate gradient method [7]),
metaheuristics (e.g., simulated annealing [8] and genetic
algorithm [9]), or other techniques [10]. While all the
grids can only have the same beam weight at a time,
the obtained fluence map should be divided into sev-
eral apertures by MLC sequencing methods [11]. As
illustrated in Fig. 2, the fluence map consists of three
apertures with different shapes, while the beam weight
in each aperture is unique.
The optimization of fluence map is relatively easy,
however, the subsequent MLC sequencing may highly
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 2

Multileaf
collimator
(MLC) Radiation
beam
Multileaf
collimator
(MLC)

Irregular therapeutic field

Electron linear accelerator Intensity-modulated radiotherapy (IMRT)
Dose-volume histogram (DVH)

Multiple f1: ‹‹—†‘•‡‘ˆͳ × × × × × × × ×

interactions × × × × × ×
f2: ƒš‹—†‘•‡‘ˆͳ
f3: ƒš‹—†‘•‡‘ˆͳ × ×
× × ×
f4: ƒš‹—†‘•‡‘ˆʹ × × × × × ×
f5: ”‡•…”‹„‡††‘•‡‘ˆͳ × × × × ×
f6: ‘•‡Ǧ˜‘Ž—‡…‘•‘ˆͳ × × × ×
ĂĂ × × × × × × × ×

Radiation treatment Solution assessment Treatment planning

Fig. 1. General procedure of intensity-modulated radiotherapy (IMRT).

Fluence map Aperture 1 and metaheuristics, just to name a few [17], [18]. So far,
× ××××××× × × × ×××× × direct aperture optimization has been a mature technique
× ×× ××× × × × ×××× ×
Grid × × × × × ×××× × and adopted in commercial systems [19].
× × × × × × ×× × Nevertheless, IMRT planning in clinical practice still
× ×× ××× × × × ×× ×
× ×× ×× × × × ×××× × requires much human expertise and takes hours or
Therapeutic
field
× ×× × × × × ×××× × even days for one clinical case [20]. Once the doctor
× ××××××× × × × ×××× × decides the treatment protocol, the medical physicist first
builds an optimization model and obtains its optimal
Aperture 3 Aperture 2 solution (i.e., treatment plan) via a planning method,
× ××××××× × × ×× ××× × then discusses with the doctor the quality of the plan
× ×× ××× × × ×× ××× ×
× × × × × ×× × according to the dose-volume histogram. If the plan
× × × × × × × × is not clinically acceptable, the medical physicist must
× ×× ××× × × × ×× × build a new model and re-run the planning method.
× ×× ×× × × × × ×
× ×× × × × ×× ××× × This procedure will probably be repeated many times
× ××××××× × × ×× ××× × as shown in Fig. 1, which is relatively time-consuming
since only one plan is obtained at a time.
Fig. 2. An illustrative example of MLC sequencing.
On the other hand, IMRT planning is naturally a
multi-objective optimization problem since the radiation
deteriorate the effectiveness since complex fluence maps damages both tumor and healthy cells [20]. To ensure the
cannot be accurately divided into few apertures [12]. By minimum doses of tumor cells and limit the maximum
contrast, some other IMRT planning methods directly doses of healthy cells, multiple conflicting objectives
optimize the shapes and beam weight of each aperture, should be optimized simultaneously. While most opti-
which is known as direct aperture optimization [13]. mizers adopted in existing planning methods are only
While the optimization problem contains a large number for single-objective optimization, the multiple objectives
of discrete variables (i.e., MLC leaf positions) and con- have to be aggregated by different weights. To determine
tinuous variables (i.e., beam weights), it is ineffective to the optimal weights for the objectives, an optimizer
directly optimize all of them by using the optimizers at should be employed many times to obtain the optimal
hand. To address this dilemma, some methods limit the solution for each setting of weights [21], [22]. In short,
shapes of apertures to certain ones [12], some methods the optimization process is also inefficient since only one
optimize the MLC leaf positions by random search [13] solution is obtained at a time.
or enumeration [14], some methods iteratively add new Therefore, the efficiency of IMRT planning can be
apertures and optimize only the beam weights [15], [16], considerably improved by generating multiple diverse
and some methods optimize the beam weights and MLC plans at a time, where ample alternatives are provided
leaf positions by mathematical programming methods to alleviate the uncertainty in both modeling and weight-
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 3

ing. Although multi-objective evolutionary algorithms of voxel v in terms of the i-th grid in the therapeutic
(MOEAs) have been applied to a variety of applications field of a beam. Besides, the intensity yi of the grid is
with large numbers of decision variables [23], [24], few determined by the beam weights and MLC leaf positions
of them have been adopted in IMRT planning. This of all the apertures related to a beam:
is because existing MOEAs mainly focus on continu- ∑
ous optimization, whereas little attention has been paid yi = wj pij , (2)
to large-scale combinatorial optimization problems like j

IMRT planning. The discrete variables in IMRT planning
pose stiff challenges for existing MOEAs to find well-
converged and diversified solutions [25]. Hence, this
paper aims to improve the efficiency of IMRT planning
by customizing an MOEA, which can obtain a set of solu-
tions that present diverse trade-offs between the multiple
conflicting objectives in IMRT planning. Specifically, this
paper includes the following three contributions:
1) The IMRT planning is formulated into a large-scale
combinatorial many-objective optimization prob-
lem. The problem definition is applicable to dif-
ferent clinical cases, where medical physicists only
need to vary the parameters in the problems.
2) A coevolutionary algorithm is proposed for solving
the above problem, termed MOEA/IMRT. In or-
der to handle the high-dimensional discrete search
space, the proposed algorithm evolves one popula-
tion with fine encoding and evolves another popu-
lation with rough encoding, where the balance be-
tween exploitation and exploration can be achieved
by the cooperation of the two populations. Besides,
two local search strategies are suggested to repair
invalid solutions and accelerate the convergence.
3) The effectiveness of the proposed MOEA/IMRT
is tested on six clinical cases of different can-
cers. According to the experimental results, the
proposed algorithm has better convergence and
diversity performance than state-of-the-art MOEAs
and IMRT planning methods.
The rest of this paper is organized as follows. Section II
gives the proposed optimization model, and reviews ex-
isting multi-objective IMRT planning methods and large-
scale MOEAs. Section III describes the proposed MOEA
for IMRT planning. Section IV analyzes the experimental
results. Lastly, Section V draws the conclusion.
where wj denotes the beam weight of the j-th aperture,
pij = 0 indicates that the i-th grid is shielded by the
MLC in the j-th aperture, and pij = 1 otherwise.
Based on the doses of voxels in PTV and OAR, a
variety of objective functions have been formulated to
describe the treatment protocol [7], [14], [26]–[29]. This
paper adopts the following four types of objective func-
tions to be minimized, which are easy to calculate and
contain just a few parameters that should be predefined
by medical physicists.
Minimum Dose: This objective function is to ensure the
minimum dose of each voxel, which is defined as:
1 ∑
M inDose(x, V, dmin ) = (max{0, dmin − dv })2 ,
|V |
v∈V
(3)
where x is a solution determining the values of wj and
pij in (2). Besides, V denotes a region of PTV or OAR and
dmin denotes the predefined minimum dose. Obviously,
the value of M inDose is zero only when all doses are
greater than or equal to dmin .
Maximum Dose: This objective function is to limit the
maximum dose of each voxel, which is defined as:
1 ∑
M axDose(x, V, dmax ) = (max{0, dv − dmax })2 ,
|V |
v∈V
(4)
where dmax denotes the predefined maximum dose.
Similarly, the value of M axDose is zero only when all
doses are less than or equal to dmax .
Prescribed Dose: This objective function is to make the
doses of all voxels as close to the prescribed dose as
possible, which is defined as:
1 ∑
P reDose(x, V, dpre ) = (dv − dpre )2 , (5)
|V |
v∈V

where dpre denotes the prescribed dose, and the value of

II. M ULTI -O BJECTIVE IMRT P LANNING P reDose is zero only when all doses are equal to dpre .
A. Problem Formulation Dose-Volume Constraint: This objective function is to
limit the maximum doses of all voxels, which is defined
The core task in IMRT planning is to find the optimal
as:
beam weights and MLC leaf positions for all the aper-
tures, so that the resultant doses of voxels in PTV (i.e., 1 ∑
DV C(x, V, ddvc , r) = (max{0, dv − ddvc })2
the planning tumor volume consisting of tumor cells) |V | (6)
v∈V
and OAR (i.e., the organ at risk consisting of healthy · (max{0, dr − dv }),
cells) meet the requirement of a clinical case. The dose
dv of a voxel can be calculated by [7], [26] where ddvc denotes the predefined maximum dose, dr
∑ denotes the r-th largest dose in V , and the value of DV C
dv = Div yi , (1) is zero only when the number of doses greater than ddvc
i is less than or equal to r.
where D is the dose deposition matrices obtained in ad- Considering all the regions in PTV and OAR, there
vance [7] and Div denotes the dose deposition coefficient may exist dozens of objective functions for one clinical
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR
case. While existing work aggregates all the objectives
into one objective [7], [14], [26], [29] or two objectives
[27], [30], this paper builds the following large-scale
combinatorial many-objective optimization problem by
aggregating only similar objectives:
Minimize f (x) = (f1 (x), . . . , f5 (x))
∑ contrary, a few MOEAs have also been adopted in IMRT
f1 (x) = M inDose(x, V, dmin )
V ∈P T V
∑
f2 (x) = M axDose(x, V, dmax )
V ∈P T V
∑ NSGA-II [36] was directly applied to the IMRT planning
+ DV C(x, V, ddvc , r)
V ∈P T V , (7)
∑ performance of NSGA-II was enhanced by a tailored
f3 (x) = M axDose(x, V, dmax )
V ∈OAR
∑ generated by a gradient based algorithm.
f4 (x) = DV C(x, V, ddvc , r)
V ∈OAR
∑
f5 (x) = P reDose(x, V, dpre )
V ∈P T V
where x is a solution containing all the beam weights
and MLC leaf positions, P T V is the set of all regions
in PTV, and OAR is the set of all regions in OAR. The
first objective f1 is the core objective, which defines the
minimum dose of PTV and ensures the effectiveness of
radiotherapy. The second objective f2 contains the maxi-
mum dose and dose-volume constraint of PTV, which
are aggregated into a single objective since they are
positively correlated with each other. The third objective
f3 defines the maximum dose of OAR and the fourth
objective f4 defines the dose-volume constraint of OAR,
and the last objective f5 defines the prescribed dose of
PTV, which makes the doses of voxels uniform so that
the plan is more practical.
Given a treatment protocol, the medical physicist
should first define the parameters dmin , dmax , dpre , ddvc ,
and r for each region V , then optimize the above prob-
lem via an IMRT planning method or other optimizer.
In the next two subsections, some state-of-the-art IMRT
planning methods and MOEAs are reviewed.
B. Existing Methods for Multi-Objective IMRT Planning
In spite of the multiple conflicting objectives in IMRT
planning, existing planning methods are mostly based
on single-objective optimization algorithms due to their
fast convergence speed. While most planning methods
aggregate the multiple objectives into a single one via the
weights set by hand, some other methods focus on the
adaptive detection of the optimal weights. For example,
some work only searches for the optimal solutions for
each single objective [31], some work samples several
sets of weights and obtains the optimal solution for each
of the aggregated objectives [21], some work aggregates
the objectives via principal component analysis [32],
some work navigates over the Pareto front by interpola-
tion between pre-found solutions [22], [33], some work
converts the original problem into several constrained
4
single-objective optimization problems [34], [35], and
some work searches for the optimal weights via particle
swarm optimization [28].
Although the above methods involve the concepts of
“multi-objective optimization” and “Pareto optimality”,
they can only find a single solution at a time. On the
planning to find multiple solutions simultaneously. In
[30], a multi-objective particle swarm optimization algo-
rithm was employed for the IMRT planning with two
objectives. In [27], a classical evolutionary algorithm
with multiple objectives and constraints. In [25], the
initialization strategy, where the initial solutions are
As a consequence, existing IMRT planning methods
can hardly strike a balance between efficiency and effec-
tiveness. On the one hand, the methods based on single-
objective optimization should be performed many times
to generate a set of diverse plans, which is very inef-
ficient in clinical practice. On the other hand, although
a few methods adopt classical MOEAs to find multiple
plans in a single run, their effectiveness has not been
fully verified via comparative studies. More importantly,
no state-of-the-art MOEA has been adopted and no
search strategy has been tailored for IMRT planning.
To take full advantage of evolutionary multi-objective
optimization in IMRT planning, this paper proposes a
new MOEA with several customized strategies, includ-
ing a coevolutionary framework and two local search
strategies. In Section IV, some state-of-the-art MOEAs
will be tested in the experiments, which are verified to
be underperformed by the proposed algorithm.
C. Existing Large-Scale MOEAs
The proposed optimization problem is characterized
by many objectives, large number of decision variables,
and discrete search space. After decades of development,
MOEAs are able to handle many objectives via enhanced
dominance relations [37], diversity based selection [38],
objective decomposition [39], or performance indicators
[40]. However, due to the black-box search paradigms of
MOEAs, most of them encounter difficulties in handling
a large number of decision variables. To tackle the curse
of dimensionality of decision space, some MOEAs based
on decision variable grouping, decision space reduction,
or novel search strategies have been proposed in recent
years [24]. The decision variable grouping based MOEAs
adopt the divide-and-conquer strategy that divides the
decision variables via different grouping strategies, such
as random grouping [41], [42], differential grouping
[43], and variable clustering [44]. The decision space
reduction based MOEAs aim to directly reduce the num-
ber of decision variables via different dimensionality
reduction methods, such as problem transformation [45],
problem reformulation [46], and unsupervised neural
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR
networks [47]. The novel search strategy based MOEAs
suggest new reproduction operators to accelerate the
convergence, such as competitive swarm optimizer [48],
self-evaluation evolution [49], and generative adversarial
networks [50]. These MOEAs have shown obvious supe-
riority over classical ones in solving a variety of large-
scale multi-objective optimization problems [51].
Nevertheless, they cannot be directly applied to IMRT
planning since all the three categories of search strate-
gies are tailored for large-scale continuous optimization,
which are unsuitable for handling the discrete variables
in IMRT planning. More seriously, the discrete variables
in IMRT planning cannot be arbitrary due to the re-
striction of aperture shapes, which even makes existing
MOEAs difficult to generate valid solutions. To address
these issues, the proposed algorithm suggests a novel
coevolutionary framework for IMRT planning. Different
from the above MOEAs handling a large number of
decision variables via variable grouping, dimensionality
reduction, or new reproduction operators, the proposed
coevolutionary framework handles the large number of
discrete variables from a new perspective. More specif-
ically, two populations with different encoding schemes
are evolved cooperatively, where one population with
fine encoding is responsible for local exploitation, and
the other population with rough encoding is responsible
for global exploration. In the next section, the detailed
procedure of the proposed algorithm is elaborated.
III. T HE P ROPOSED A LGORITHM
A. Encoding Scheme of MOEA/IMRT
To solve the optimization problem defined in (7), any
MOEAs for continuous optimization (e.g., the genetic
algorithm based on simulated binary crossover [52] and
polynomial mutation [53]) can be adopted in theory,
where the decision variables of MLC leaf positions only
need to be rounded to the nearest integers before func-
tion evaluation. However, the proposed optimization
problem provides the following difficulties that hinder
MOEAs from reaching the global Pareto front:
• Flat regions in landscape: According to the definitions
in (3)–(6), the landscapes of minimum dose, maximum
dose, and dose-volume constraint contain large flat re-
gions due to the operator max, making the proposed
optimization problem difficult to be optimized.
• Discrete variables: Since the proposed optimization
problem has a discrete search space, the rounding
of real variables will introduce many small flat
regions in the landscape, and hence the evolution
of a population will become more challenging.
• Restriction of variables: Due to the physical limitation,
the aperture shapes can neither be too small nor
disconnected, which means that many of the ran-
domly generated solutions are invalid and imprac-
tical. Hence, the search space becomes discrete even
if real variables are optimized instead of integers.
5
Fine encoding
Rough encoding
x2 = 3 x4 = 5
x1 = 4 × × × × × × × × x2 = 4 × × × × × × × ×
x3 = 3 × × × × × × x4 = 3 × × × × × × × ×
x5 = 1 × × x 6 = 1 x1 = 3 × × × × ×
x7 = 2 × × × x8 = 1 × × × × ×
x9 = 3 × × × × × × x10 = 3 × × × × ×
x11 = 3 × × × × × x12 = 2 × × × × ×
x13 = 3 × × × × x14 = 1 x3 = 3 × × × × ×
x15 = 4 × × × × × × × × x16 = 4 × × × × × × × ×
Beam weight: x17 = 0.8 Beam weight: x5 = 0.8
Fig. 3. An illustrative example of two encoding schemes used in the
proposed algorithm. A solution may encode dozens of such apertures.
As a consequence, most MOEAs are likely to converge
slowly or even get trapped into local optimums, since the
proposed optimization problem has a high-dimensional
discrete search space and massive flat regions. To im-
prove the exploration ability, the proposed MOEA/IMRT
suggests a coevolutionary framework, in which two
different encoding schemes are used simultaneously.
Fig. 3 illustrates the fine encoding and rough encoding
used in the proposed MOEA/IMRT. As can be observed,
the fine encoding directly encodes the positions of all
MLC leaves (i.e., x1 , . . . , x16 ) and the weight of beam
(i.e., x17 ) for each aperture, while the rough encoding
encodes the aperture shape (i.e., left x1 , up x2 , width
x3 , and height x4 ) and the weight of beam (i.e., x5 ). The
fine encoding is straightforward and has been used in
existing IMRT planning methods, which can represent
any possible aperture shapes; by contrast, the rough
encoding can only represent rectangular shapes. On the
other hand, the fine encoding contains much more de-
cision variables than the rough encoding, which means
that the former is harder to be optimized than the latter.
That is, a population with fine encoding has good
exploitation ability and is responsible for approximating
the Pareto front, and a population with rough encoding
has good exploration ability and can escape from local
optimums. Therefore, the exploitation and exploration
can be balanced by the cooperation of two populations
with different encoding schemes, where the convergence
of the population with fine encoding can be significantly
accelerated by the evolution of the population with
rough encoding. Fig. 4 plots the first two objectives
of the populations on the Esophagus dataset, where
the populations are collected at different generations
of the proposed MOEA/IMRT with fine encoding and
both the two encoding schemes, and the experimental
settings are referred to Section IV-A. It is obvious that
the algorithm with fine encoding converges quite slowly
after 10000 function evaluations, while the algorithm
with both fine encoding and rough encoding can de-
crease the objective values steadily and obtain much
better solutions at last. Furthermore, Fig. 5 depicts the
convergence profiles of hypervolume (HV) [54] values
obtained by MOEA/IMRT with a single and two en-
coding schemes on the same dataset, averaged over 30
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 6

MOEA/IMRT with fine encoding

Algorithm 1: Procedure of MOEA/IMRT
100 evaluations

10 0 10 000 evaluations
100 000 evaluations
Input: N (population size), K (number of exchanged
200 000 evaluations solutions)
Output: P1 (final population)
10-2
1 P1 ← Randomly generate N solutions of fine encoding;
2 P2 ← Randomly generate N solutions of rough encoding;
f2

3 [P1 , P2 ] ← LocalSearchA(P1 , P2 );
-4
4 while termination criterion is not fulfilled do
10
5 P1′ ← Select N parents from P1 via binary tournament
selection;
6 O1 ← Generate offsprings based on P1′ ;
10-6
10
-4
10
-3
10
-2
10
-1 7 P2′ ← Select N parents from P2 via binary tournament
f1 selection;
MOEA/IMRT with fine encoding and rough encoding 8 O2 ← Generate offsprings based on P2′ ;
100 evaluations 9 [O1 , O2 ] ← LocalSearchA(O1 , O2 );
100
10 000 evaluations 10 [O1′ , O2′ ] ← Exchange(O1 , O2 , K);
P1 ← P1 ∪ O1 ∪ O1′ ;
100 000 evaluations
200 000 evaluations 11
12 P2 ← P2 ∪ O2 ∪ O2′ ;
-2 13 P1 ← Truncate P1 via environmental selection;
10
14 P2 ← Truncate P2 via environmental selection;
f2

15 P1 ← LocalSearchB(P1 );
10
-4 16 return P1 ;

10-6
-4 -3
10 10 10
f1
Fig. 4. Comparison between the first two objectives of the populations
on the Esophagus dataset, which are collected at different generations
of the proposed algorithm with fine encoding and both the two
encoding schemes.
1 respectively. Then, the mating pools are used to gener-
0.95
0.9
0.85
0.8
1 2 3 4
Number of evaluations
Fig. 5. Convergence profiles of mean HV obtained by MOEA/IMRT
with a single and two encoding schemes on the Esophagus dataset.
runs. According to the figure, the algorithm with rough
encoding converges much faster than the algorithm with
fine encoding since the rough encoding has a better
exploration ability. However, the algorithm with rough
encoding converges prematurely and finally obtains the
worst HV value, since it cannot represent irregular aper-
ture shapes to further reduce the objective values. By
contrast, the algorithm with fine encoding obtains better
result due to its good exploitation ability. Therefore, by
adopting both the rough encoding and fine encoding,
the proposed MOEA/IMRT has good exploration ability
and good exploitation ability at the same time, leading
to the fastest convergence speed and the best HV value.
B. General Procedure of MOEA/IMRT
The procedure of the proposed MOEA/IMRT is pre-
sented in Algorithm 1. To begin with, a population P1
-2 -1
having N solutions with fine encoding and a popula-
10
tion P2 having N solutions with rough encoding are
randomly initialized, and the first local search strat-
egy LocalSearchA() is conducted on the two popula-
tions to repair invalid solutions. At each generation of
MOEA/IMRT, two mating pools P1′ and P2′ are first
constructed by selecting N solutions from P1 and P2 ,
ate two offspring population O1 and O2 via simulated
binary crossover and polynomial mutation, and the off-
springs are also repaired by the first local search strat-
egy. Afterwards, in the operation of offspring exchange
Fine encoding Exchange(), some offsprings with fine encoding in O1
Rough encoding
Rough + fine encoding are converted into solutions with rough encoding and
stored in O2′ , and some offsprings with rough encoding
5
105
in O2 are converted into solutions with fine encoding and
stored in O1′ . Lastly, the population P1 is combined with
O1 ∪ O1′ and truncated by environmental selection, and
the population P2 is combined with O2 ∪ O2′ and also
truncated by environmental selection. Besides, the sec-
ond local search strategy LocalSearchB() is conducted
on P1 for further enhancement of the convergence.
For the selection strategies in the proposed
MOEA/IMRT, the mating selection and environmental
selection in SPEA2 [55] with shift-based density
estimation [38] are adopted for simplicity, which are
flexible to be embedded in different MOEAs and
have demonstrated high effectiveness in handling many
objectives. For the exchange of offsprings, MOEA/IMRT
converts between the solutions with fine encoding and
rough encoding by the steps given in Algorithm 2.
Firstly, some solutions are separately selected from the
two offspring populations to be exchanged, which is
achieved by the same strategy as the environmental
selection of MOEA/IMRT. Note that only K solutions
rather than all the solutions are selected here, since
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 7

Algorithm 2: Exchange(O1 , O2 , K) Rough encoding

Fine encoding
y2 = 2 y4 = 6
Input: O1 (offsprings with fine encoding), O2 (offsprings x1 = 4 × × × × × × × × x2 = 4 × × × × × × × ×
with rough coding), K (number of exchanged x3 = 3 × × × × × × x4 = 3 y1 = 4 × × × × ×
solutions) x5 = 1 × × x6 = 1 × × × × ×
Output: O1′ (converted offsprings with fine encoding), O2′ x7 = 2 × × × x8 = 1 Convert × × × × ×
(converted offsprings with rough coding) x9 = 3 × × × × × × x10 = 3 × × × × ×
1 O1K ← Select K solutions from O1 via environmental selection; x11 = 3 × × × × × x12 = 2 × × × × ×
2 O2K ← Select K solutions from O2 via environmental selection; x13 = 3 × × × × x14 = 1 y3 = 3 × × × × ×
//Convert fine encoding into rough encoding x15 = 4 × × × × × × × × x16 = 4 × × × × × × × ×
3 O2′ ← ∅; Beam weight: x17 = 0.8 Beam weight: y5 = 0.8
4 foreach solution p ∈ O1K do Rough encoding
5 q ← ∅; y2 = 3 y4 = 5
Fine encoding
6 foreach aperture x ∈ p do × × × × × × × × x1 = 4 × × × × × × × × x2 = 4
7 Convert x into y by (8); × × × × × × × × x3 = 4 × × × × × × × × x4 = 4
8 q ← q ∪ {y}; y1 = 3 × × × × × x5 = 2 × × × × × x6 = 3
9 O2′ ← O2′ ∪ {q}; × × × × × Convert x7 = 2 × × × × × x8 = 3
× × × × × x9 = 2 × × × × × x10 = 3
//Convert rough encoding into fine encoding
× × × x12 = 3
O1′ ← ∅;
× × × × × x11 = 2 × ×
10
y3 = 3 × × × × × x13 = 2 × × × × × x14 = 3
11 foreach solution q ∈ O2K do
× × × × × × × × x15 = 4 × × × × × × × × x16 = 4
12 p ← ∅;
Beam weight: y5 = 0.8 Beam weight: x17 = 0.8
13 foreach aperture y ∈ q do
14 Convert y into x by (9);
15 p ← p ∪ {x}; Fig. 6. An illustrative example of the conversion between fine encoding
and rough encoding.
16 O1′ ← O1′ ∪ {p};
17 return O1′ and O2′ ; (x1 , x2 , . . . , xd ) with fine encoding by
⌈c⌉
x2i−1 = , i < y2 or i ≥ y2 + y4
the exchanged solutions need to be re-evaluated 2
and consume additional computational resource. A x2i−1 = y1 − 1, y2 ≤ i < y2 + y4
⌊c⌋
parameter sensitivity analysis of K will be performed x2i = , i < y2 or i ≥ y2 + y4 . (9)
in Section IV-C. After selecting some solutions from 2
the offspring populations, the encoding scheme of x2i = c − y1 − y3 + 1, y2 ≤ i < y2 + y4
each selected solution is changed. As illustrated in xd = y5
Fig. 6, the aperture shape is smoothed when a solution As a consequence, the proposed MOEA/IMRT sep-
with fine encoding is converted into rough encoding, arately evolves two populations with different encod-
while the aperture shape keeps unchanged when a ing schemes by using the same strategies, and reaches
solution with rough encoding is converted into fine cooperation between the two populations by sharing
encoding. Formally, for a solution p with fine encoding, all the offsprings. The proposed coevolutionary frame-
its decision variables x = (x1 , x2 , . . . , xd ) corresponding work is different from existing ones in terms of two
to each aperture are converted into y = (y1 , y2 , . . . , y5 ) aspects: Firstly, existing coevolutionary frameworks for
with rough encoding by many-objective optimization hold a strong cooperation
between multiple populations, where the populations
⌈ ⌉ cooperate in mating selection, offspring generation, and
1 ∑
rear
y1 = x2i−1 + 1 environmental selection [56], [57]; by contrast, the pro-
rear − head + 1 posed framework holds a weak cooperation that only
i=head
y2 = head shares the offsprings generated by all the populations,
⌈ ⌉ where each population is evolved without the distur-
1 ∑
rear
, (8)
y3 = c − y1 − x2i + 1 bance of other populations and can better spread along
rear − head + 1 the whole Pareto front [58]. Secondly, existing coevolu-
i=head
y4 = rear − head + 1 tionary frameworks for large-scale optimization evolve
y5 = xd multiple populations with the same encoding scheme,
where each population corresponds to different part of
the decision variables [41], [44]; by contrast, the encoding
where d is the number of decision variables of each schemes of the populations are different in the proposed
aperture represented by fine encoding, c is the num- framework, which can better balance between exploita-
ber of columns in an aperture, and head and rear are tion and exploration.
the indexes of the first and last rows where the MLC There also exist some large-scale MOEAs using two
leaves are opened, respectively. As for a solution q with encoding schemes, where some solutions use the original
rough encoding, its decision variables y = (y1 , y2 , . . . , y5 ) encoding of a continuous MOP and some others use a
corresponding to each aperture are converted into x = shortened encoding to accelerate the convergence. For
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 8

Fine encoding Fine encoding

(Very small shape) (Repaired)
Algorithm 3: LocalSearchA(P1 , P2 )
× × × ××××× × × ×××××× Input: P1 (population with fine encoding), P2 (population
× × × ××××× × × ×××××× with rough encoding)
× × × ××××× × × ×××××× Output: P1 (repaired population with fine encoding), P2
× × × × ×× Repair
× × × × (repaired population with rough encoding)
× × × ×× × × × //Repair apertures in fine encoding
1 foreach solution p ∈ P1 do
× × × × ××× × × × ×× 2 foreach aperture x ∈ p do
× × × ××××× × × ×××××× 3 Repair x by (10);
× × × ××××× × × ××××××
Fine encoding Fine encoding //Repair apertures in rough encoding
(Disconnected shape) (Repaired) 4 foreach solution q ∈ P2 do
× × ××× ××× × × ××× ××× 5 foreach aperture y ∈ q do
× × × ××× × × × ××× 6 Repair y by (11);
× × ×× ××× Repair
× × × ××× 7 return P1 , P2 ;
× × ×× ×× × × ×× ××
× × ××× ××× × × × ×××
× × × ××× × × × ×××
× × ××× ××× × × ××× ××× each aperture are repaired by
× × ××× ××× × × ××× ××× x2i = min{x2i , c − x2i−1 }, 1 ≤ i ≤ r
{ ⌈ ⌉}
Rough encoding Rough encoding Smin − S
(Very small shape) (Repaired) x2i−1 = x2i−1 − max 0, ,
2(rear − head + 1)
× × × ×××× × × × × ××××× head ≤ i ≤ rear
× × × ×××× × × × × ××××× { ⌈ ⌉}
× × × ×××× × × × × ×× Smin − S , (10)
x2i = x2i − max 0, ,
× × × × × Repair
× × × ×× 2(rear − head + 1)
× × × × × × × × ×× head ≤ i ≤ rear
× × × ×××× × × × × ×× x2i−1 = min{x2i−1 , c − x2(i−1) − 1}, head < i ≤ rear
× × × ×××× × × × × ×××××
× × × ×××× × × × × ××××× x2i = min{x2i , c − x2(i−1)−1 − 1}, head < i ≤ rear

where c is the number of columns in an aperture, r is

Fig. 7. An illustrative example of the local search strategy for repairing
invalid solutions.
the number of rows in an aperture, Smin is the threshold
of small aperture, S is the number of opened grids in
the aperture, and head and rear are the indexes of the
example, the encoding is shortened by a weighted opti-
first and last rows where the MLC leaves are opened,
mization framework in [45], a linear search mechanism
respectively. In (10), the first formula ensures that each
in [59], and unsupervised neural networks in [47]. It
pair of MLC leaves do not intersect each other, the
should be noted that the idea of the proposed two
second and third formulas expand small apertures, and
encoding schemes is different from existing ones, as the
the last two formulas repair disconnected apertures. On
former is tailored for IMRT planning while the latter are
the other hand, for each solution q with rough encoding,
generic strategies for continuous black-box optimization.
its decision variables y = (y1 , y2 , . . . , y5 ) corresponding
Section IV-B will verify the superiority of the proposed
to each aperture are repaired by
algorithm by comparing it with existing coevolutionary
{ ⌈ ⌉}
algorithms and those with two encoding schemes. Smin − S
y1 = y1 − max 0, , rand ≤ 0.5
2y4
{ ⌈ ⌉}
Smin − S
y3 = y3 + max 0, , rand ≤ 0.5
y4
{ ⌈ ⌉} , (11)
C. Local Search Strategies of MOEA/IMRT Smin − S
y2 = y2 − max 0, , rand > 0.5
2y3
Although the bi-encoding coevolutionary framework { ⌈ ⌉}
Smin − S
is more suitable for IMRT planning than existing y4 = y4 + max 0, , rand > 0.5
y3
MOEAs, it is not efficient enough to find a set of diverse
plans. Therefore, two local search strategies are proposed where rand denotes a random number uniformly sam-
for a further enhancement of efficiency. As detailed in pled in [0, 1]. Since an aperture represented by rough
Fig. 7 and Algorithm 3, the first local search strategy encoding is always a connected rectangle, (11) only
LocalSearchA() is to ensure the clinical practicality of needs to expand small apertures along the vertical or
solutions, where all the aperture shapes in each solution horizontal direction with the same probability.
cannot be disconnected or too small (i.e., the number The second local search strategy LocalSearchB() aims
of opened grids is less than a predefined threshold). to enhance the population P1 with fine encoding by
To this end, for each solution p with fine encoding, its optimizing the beam weights. Represented by real vari-
decision variables x = (x1 , x2 , . . . , xd ) corresponding to ables, the beam weights are easier to optimize than the
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 9

TABLE I
D ETAILED I NFORMATION A BOUT S IX D ATASETS U SED IN THE E XPERIMENTS

Parameters Sneezer Renal RightLung Throat Cervical Esophagus

Number of M inDose()
Number of M axDose()
Planning tumor volume (PTV)
Number of P reDose()
Number of DV C()
Number of M axDose()
Organ at risk (OAR)
Number of DV C()
Numbers of beams
Numbers of apertures for each beam
Number of rows of apertures for each beam
Number of decision variables for rough coding
Number of decision variables for fine coding
5 2 2 2 3 1
5 2 2 2 2 1
1 2 2 2 2 1
5 2 2 2 3 1
17 3 1 10 8 1
1 2 6 4 11 4
7 5 5 6 7 5
6, 7, 5, 8, 7, 7, 8 9, 8, 12, 12, 9 10, 10, 9, 10, 11 8, 9, 8, 5, 8, 8 7, 6, 8, 6, 7, 8, 8 10, 11, 10, 10, 9
24, 24, 24, 24, 24, 24, 24 23, 23, 23, 23, 22 27, 28, 27, 27, 27 21, 21, 21, 21, 21, 21 30, 30, 30, 30, 30, 30, 30 21, 21, 21, 21, 21
240 250 250 230 250 250
2352 2332 2770 1978 3050 2150

Algorithm 4: LocalSearchB(P1 ) RVEA are effective MOEAs tailored for many-objective

Input: P1 (population with fine coding)
Output: P1 (optimized population with fine coding)
1 PN ← Non-dominated solutions in P1 ;
2 W ← Randomly generate a population with only beam
weights;
3 Randomly select a solution from PN for each solution in
W , then evaluate W ;
4 while termination criterion is not fulfilled do
5 W ′ ← Select parents from W via binary tournament
selection;
6 O ← Generate offsprings based on W ′ ;
7 Randomly select a solution from PN for each solution
in O, then evaluate O;
8 W ← W ∪ O;
9 W ← Truncate W via environmental selection;
10 P1 ← P1 ∪ W ;
11 P1 ← Truncate P1 via environmental selection;
12 return P1 ;
aperture shapes, however, they interact with the aperture
shapes and may not be well optimized. Therefore, this
local search strategy merely optimizes all the beam
weights in the solutions. In fact, some existing IMRT
planning methods only optimize the beam weights for
simplicity [7], [26], [29]. As described in Algorithm 4,
the optimization of beam weights employs the same
selection strategies and genetic operators as the main
framework of MOEA/IMRT. Since a solution consisting
of beam weights cannot be evaluated, each solution is
integrated with the aperture shapes of a non-dominated
solution randomly selected from P1 . After the optimiza-
tion of beam weights, the final population is combined
with P1 and truncated by environmental selection. This
local search strategy is performed with a population size
of 20 and 2000 function evaluations after every 100 gen-
erations of MOEA/IMRT, which does not consume much
computational resource. Instead, it brings a significant
performance improvement as verified in Section IV-C.
IV. E XPERIMENTAL S TUDIES
The proposed MOEA/IMRT is compared with eight
representative algorithms in the experiments, including
Two Arch2 [57], RVEA [60], CCGDE3 [41], WOF-SMPSO
[45], LMOCSO [48], Cotrutz’s algorithm [61], Cao’s algo-
rithm [62], and Wang’s algorithm [14]. Two Arch2 and
optimization, where Two Arch2 has a coevolutionary
framework and RVEA is based on objective decom-
position. CCGDE3, WOF-SMPSO, and LMOCSO are
large-scale MOEAs based on variable grouping, decision
space reduction, and novel search strategy, respectively;
besides, WOF-SMPSO adopts two encoding schemes.
Cotrutz’s algorithm and Wang’s algorithm are direct
aperture optimization methods based on genetic algo-
rithm and conjugate gradient, respectively, and Cao’s
algorithm is a two-step optimization method based on
conjugate gradient.
A. Parameter Settings
1) Datasets: The compared algorithms are tested on six
real-world tumor cases, including sneezer, renal, right
lung, throat, cervical, and esophagus cancers. For each
case, the medical physicist has defined the number of
beams, the number of apertures for each beam, the size
of each aperture, and a number of objective functions
with corresponding parameters for the regions in PTV
and OAR. Detailed information about these datasets is
presented in Table I, where the number of real variables
varies from 230 to 250 for rough encoding and varies
from 1978 to 3050 for fine encoding.
2) Parameters in Algorithms: The parameters in the
compared algorithms are set as suggested in their origi-
nal papers. In RVEA, the rate of change of penalty is set
to 2 and the frequency of reference vector adaptation is
set to 0.1. In CCGDE3, the number of groups is set to 2
and the size of each subpopulation is set to 40. In WOF-
SMPSO, the variables are divided into 4 groups by or-
dered grouping and aggregated by interval-intersection
transformation, the number of evaluations for original
problem is set to 1000, the number of evaluations for
transformed problem is set to 500, and the fraction
of function evaluations for transformed problem is set
to 0.5. In the proposed MOEA/IMRT, the number of
exchanged solutions K is set to 10. As for the reproduc-
tion operators, Two Arch2, RVEA, Cotrutz’s algorithm,
and MOEA/IMRT use simulated binary crossover [52]
and polynomial mutation [53], where the probability of
crossover is set to 1, the probability of mutation is set
to 1/D (D is the number of decision variables), and the
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 10

1 1 1
Dose-volume constraint
Relative volume (%)

Relative volume (%)

Relative volume (%)

0.8 Cumulative distribution 0.8 Maximum dose 0.8 (d , r ) (d ,r )
dvc1 1 dvc2 2
of the doses in PTV dmax
0.6 0.6 0.6
Maximum dose
0.4 d 0.4 0.4
max
Cumulative distribution Cumulative distribution
0.2 Minimum dose 0.2 of the doses in OAR 0.2 of the doses in OAR
dmin
0 0 0
0 1000 2000 3000 4000 0 1000 2000 3000 4000 5000 6000 0 1000 2000 3000 4000
Dose (/cGy) Dose (/cGy) Dose (/cGy)

(a) Maximum and minimum doses of PTV. (b) Maximum dose of OAR. (Ideal case: the (c) Dose-volume constraint of OAR. (Ideal
(Ideal case: the vertical part of the curve is curve is to the left of the vertical line) case: the curve is to the lower left of the
between the two vertical lines) two points)

Fig. 8. Illustration of different objectives in a dose volume histogram (DVH). A point (x, y) on the curve indicates that the ratio of doses greater
than x in the PTV or OAR is y.

distribution index is set to 20; CCGDE3 uses differential are reported. Besides, the Friedman test with Bonferroni
evolution and polynomial mutation, where both the correction [63] at a significance level of 0.05 is adopted
learning rate F and the crossover rate CR are set to for statistical test, where ‘+’, ‘−’, and ‘≈’ indicate that
0.5; WOF-SMPSO uses particle swarm optimization and the HV values obtained by an algorithm are significantly
polynomial mutation; LMOCSO uses competitive swarm better, significantly worse, and statistically similar to the
optimizer and polynomial mutation; Cao’s algorithm proposed MOEA/IMRT, respectively.
and Wang’s algorithm uses conjugate gradient method. 6) Dose-Volume Histogram (DVH): The DVH is also
3) Problem-Dependent Strategies: In spite of the differ- used to visually assess the quality of plans, which is the
ent numbers of objective functions in the datasets, they main assessment criterion used by medical physicists. A
are aggregated into five objectives by (7) and optimized DVH depicts the cumulative distribution of the doses in
by all the compared MOEAs. As for Cotrutz’s algorithm, PTV and OAR, where a point (x, y) on a curve indicates
Cao’s algorithm, and Wang’s algorithm, they aggregate that the ratio of doses greater than x in the PTV or
all the objective functions into a single one. Except OAR is y. Fig. 8 illustrates a cumulative distribution
for the proposed MOEA/IMRT adopting two encoding curve together with different objectives in a DVH, where
schemes, all the other compared algorithms represent the vertical part of the curve should be between the
solutions with fine encoding. To ensure the validity of two vertical lines of maximum and minimum doses in
the solutions, all the compared MOEAs perform the Fig. 8(a), the curve should be to the left of the vertical line
LocalSearchA() described in Algorithm 3 once an off- of maximum dose in Fig. 8(b), and the curve should be
spring is generated. Since Cotrutz’s algorithm, Cao’s to the lower left of the points of dose-volume constraint
algorithm, and Wang’s algorithm can only generate one in Fig. 8(c). If the curve does not meet any of the above
solution at a time, a set of uniformly distributed weight conditions, it implies that the plan is not optimal on the
vectors are sampled for the aggregation of objective corresponding objective.
functions, where one solution is obtained by optimizing
the single objective aggregated by each weight vector
and all the solutions constitute the final population. B. Comparisons Between MOEA/IMRT and State-of-the-Art
4) Population Size and Termination Criterion: For fair- Table II lists the HV results obtained by the nine
ness, the population size of all the compared MOEAs is compared algorithms on six datasets. It is clear that the
set to 100 and the maximum number of function evalu- proposed MOEA/IMRT obtains the best performance on
ations of all the compared MOEAs is set to 500000. Be- all the datasets, whose HV values are always signifi-
sides, Cotrutz’s algorithm, Cao’s algorithm, and Wang’s cantly better than all the other compared algorithms.
algorithm are performed 100 times and the maximum For a visual comparison, Fig. 9 compares the objective
number of function evaluations is set to 5000 each time. values of the populations with median HV obtained
5) Performance Indicator: Since the true Pareto fronts of by the proposed MOEA/IMRT and each of the other
real-world problems are unknown, the HV indicator [54] algorithms on the Esophagus dataset. It can be observed
is adopted to assess the performance of the compared that the population obtained by MOEA/IMRT has bet-
algorithms. To determine the reference point for HV ter convergence than those obtained by Two Arch2,
calculation, the non-dominated solutions obtained by CCGDE3, WOF-SMPSO, Cotrutz’s algorithm, Cao’s al-
all the algorithms in all the runs are collected, and the gorithm, and Wang’s algorithm, and has better diver-
reference point consists of the maximum objective values sity than those obtained by RVEA and LMOCSO. For
of the non-dominated solutions on all dimensions. To Two Arch2 and RVEA tailored for many-objective opti-
eliminate the influence of randomness, each algorithm mization, the convergence performance of RVEA is bet-
is performed on each dataset for 30 independent runs, ter than Two Arch2, which means that the coevolution-
where the mean and standard deviation of the HV values ary framework of Two Arch2 is ineffective for the many
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 11

TABLE II
HV R ESULTS O BTAINED BY N INE A LGORITHMS ON S IX D ATASETS OF IMRT P LANNING . T HE B EST R ESULT IN E ACH R OW IS H IGHLIGHTED

Problem Two Arch2 RVEA CCGDE3 WOF-SMPSO LMOCSO Cotrutz’s algorithm Cao’s algorithm Wang’s algorithm MOEA/IMRT

Esophagus 9.6064e-1 (8.85e-3) − 9.6384e-1 (3.75e-3) − 0.0000e+0 (0.00e+0) − 9.5540e-1 (9.52e-3) − 9.5822e-1 (1.31e-2) − 3.4490e-2 (3.22e-2) − 0.0000e+0 (0.00e+0) − 9.1906e-1 (1.00e-2) − 9.8045e-1 (2.61e-3)

Renal 9.9330e-1 (1.72e-3) − 9.8747e-1 (1.95e-3) − 0.0000e+0 (0.00e+0) − 9.7799e-1 (8.29e-3) − 9.8099e-1 (1.46e-3) − 9.0421e-1 (2.20e-2) − 0.0000e+0 (0.00e+0) − 9.8749e-1 (6.67e-4) − 9.9768e-1 (3.60e-4)

RightLung 8.8601e-1 (1.13e-2) − 7.5203e-1 (2.43e-1) − 2.4031e-2 (5.33e-2) − 7.2896e-1 (2.64e-1) − 8.4637e-1 (1.72e-2) − 4.8269e-1 (2.72e-1) − 0.0000e+0 (0.00e+0) − 7.2737e-1 (4.29e-3) − 9.0784e-1 (6.61e-3)

Sneezer 9.8459e-1 (1.41e-3) − 9.7737e-1 (1.89e-3) − 0.0000e+0 (0.00e+0) − 8.9300e-1 (1.27e-1) − 9.8122e-1 (1.06e-3) − 9.6587e-1 (5.76e-3) − 1.0271e-1 (1.41e-2) − 9.7198e-1 (2.43e-3) − 9.8680e-1 (1.10e-3)

Throat 8.4575e-1 (1.77e-2) − 5.9789e-1 (3.27e-2) − 0.0000e+0 (0.00e+0) − 5.8518e-1 (1.18e-1) − 2.2960e-1 (2.14e-1) − 0.0000e+0 (0.00e+0) − 0.0000e+0 (0.00e+0) − 0.0000e+0 (0.00e+0) − 8.5912e-1 (9.62e-3)

Cervical 9.6661e-1 (3.46e-3) − 9.6897e-1 (5.40e-3) − 1.1003e-1 (5.95e-2) − 9.2699e-1 (3.31e-2) − 9.7579e-1 (1.67e-3) − 8.4165e-1 (1.33e-2) − 0.0000e+0 (0.00e+0) − 9.4716e-1 (3.58e-3) − 9.8394e-1 (1.61e-3)

+/ − / ≈ 0/6/0 0/6/0 0/6/0 0/6/0 0/6/0 0/6/0 0/6/0 0/6/0

Fig. 9. Parallel coordinates of the objective values of the populations with median HV obtained by the compared algorithms on the Esophagus
dataset. MOEA/IMRT has better convergence performance than Two Arch2, CCGDE3, WOF-SMPSO, Cotrutz’s algorithm, Cao’s algorithm, and
Wang’s algorithm, and better diversity performance than RVEA and LMOCSO.

objectives of IMRT; besides, the reference vector based and OAR2, it can be found that all the algorithms can
selection strategy of RVEA is imperfect since it has worse almost meet the requirement of dose-volume constraints.
diversity performance than MOEA/IMRT. For CCGDE3, For the curves of OAR3, all the algorithms can mostly
WOF-SMPSO, and LMOCSO tailored for large-scale op- meet the requirement of maximum dose. As for the most
timization, the novel search strategy of LMOCSO is important curves of PTV, only RVEA, LMOCSO, and
more effective than the coevolutionary framework and the proposed MOEA/IMRT can meet the requirement of
variable grouping strategy of CCGDE3 and the two both maximum and minimum doses. The band of PTV
encoding schemes and decision space reduction strategy obtained by MOEA/IMRT between the vertical lines of
of WOF-SMPSO, since the former exhibits much better maximum and minimum doses is obviously wider than
convergence performance; besides, the diversity perfor- those obtained by RVEA and LMOCSO, which indi-
mance of LMOCSO is also worse than MOEA/IMRT. cates a better diversity performance of MOEA/IMRT.
For Cotrutz’s algorithm, Cao’s algorithm, and Wang’s In addition, Figs. S1–S5 in the Supplementary Materials
algorithm tailored for IMRT planning, they have worse show the DVH of the populations obtained on the other
convergence performance than MOEA/IMRT since the five datasets, where MOEA/IMRT can also obtain a set
aperture shapes cannot be well optimized by using ge- of well-converged and diversified solutions on all the
netic algorithm (without local search), MLC sequencing, datasets.
and enumeration, respectively.
Moreover, Fig. 10 shows the DVH of the populations
with median HV obtained by the compared algorithms C. Verification of the Core Components in MOEA/IMRT
on the Esophagus dataset. To better reflect the popula- Firstly, MOEA/IMRT is compared to a variant without
tion diversity, the range of all the curves in a population the local search strategy LocalSearchB() to verify the
rather than a single curve is plotted, where a curve effectiveness of the local search strategy for enhancing
corresponds to the cumulative distribution of the doses the population with fine encoding. According to the
in PTV or OAR of one solution. For the curves of OAR1 convergence profiles of mean HV shown in Fig. 11,
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR 12

Fig. 10. DVH of the populations with median HV obtained by the compared algorithms on the Esophagus dataset. The meanings of the elements
in the figures are referred to Fig. 8.

0.95
of the solutions obtained by MOEA/IMRT with and
without local search, where the curves corresponding
0.9
to the solution with the smallest sum of all objectives
0.85 in the population with median HV are shown. It can
0.8
be found that the two algorithms obtain the same good
With LocalSearch
Without LocalSearch curves of OAR1–OAR3, while the algorithm without
1 2 3 4 5 local search obtains a curve of PTV obviously exceeding
Number of evaluations 105
1 the maximum dose. Therefore, performing local search
With local search (PTV) Without local search (OAR2)
0.9 With local search (OAR1)
With local search (OAR2)
Without local search (OAR3)
Maximum/Minimum dose (PTV)
on the population with fine encoding can improve the
0.8 With local search (OAR3)
Without local search (PTV)
Dose-volume cons (OAR1)
Dose-volume cons (OAR2)
performance of MOEA/IMRT indeed.
0.7 Without local search (OAR1) Maximum dose (OAR3)
Then, MOEA/IMRT is compared to three variants
Relative volume (%)

0.6

0.5
with different values of K, i.e., the number of exchanged
0.4
solutions in Algorithm 2. According to the results shown
0.3
in Fig. 12, the algorithms with different values of K
0.2 gain very similar HV values, which means that the
0.1 performance of MOEA/IMRT is not sensitive to the
0
0 1000 2000 3000 4000 5000 6000 7000
setting of K. Besides, K = 10 leads to a relatively
Dose (/cGy) better performance than the other settings, hence K is
suggested to be 10 in all cases.
Fig. 11. Convergence profiles of mean HV and DVH of the solutions
obtained by MOEA/IMRT with and without local search on the Lastly, MOEA/IMRT is compared to two variants,
Esophagus dataset.
where one variant evolves only a population with rough
encoding and the other variant evolves only a popula-
the elimination of the local search strategy decreases tion with fine encoding. According to the HV results
the convergence speed of MOEA/IMRT and leads to a obtained on all the datasets given in Table SI in the
worse HV value. Besides, the figure also shows the DVH Supplementary Materials, the MOEA/IMRT with two
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. , NO. , MONTH YEAR
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.5 1 1.5 2 2.5 3 3.5 4 4.5
Number of evaluations
Fig. 12. Convergence profiles of mean HV and DVH of the populations
with median HV obtained by MOEA/IMRT with different values of
K on the Esophagus dataset.
encoding schemes obtains obviously better overall per-
formance than those with only rough encoding or fine
encoding. Hence, the effectiveness of the two encoding
schemes can be verified.
V. C ONCLUSIONS AND F UTURE W ORK
In order to improve the efficiency of IMRT planning, a
set of diverse plans are expected to be obtained in a sin-
gle optimization process. However, most existing IMRT
planning methods can only obtain a single solution at a
time, and existing MOEAs can hardly be employed due
to their poor performance on large-scale combinatorial
many-objective optimization problems. Therefore, this
paper has proposed a new MOEA for IMRT planning,
which tackles the high-dimensional discrete search space
of IMRT planning by suggesting a bi-encoding coevolu-
tionary framework and two local search strategies. Ex-
perimental results have demonstrated that the use of two
encoding schemes can well balance between exploitation
and exploration, and the local search strategies can
further improve the convergence speed. In comparison
to state-of-the-art algorithms, the proposed algorithm
exhibits better convergence and diversity performance
on various clinical cases.
Mathematical programming methods have fast con-
vergence speed but can obtain only one solution in a
single run, while MOEAs have relatively slow conver-
gence speed but can obtain multiple solutions simultane-
ously. Although the proposed MOEA has demonstrated
high effectiveness in IMRT planning, it is reasonable to
take full advantage of both mathematical programming
methods and MOEAs for achieving better convergence
and diversity performance in the future. In addition, it is
desirable to build more complex optimization models to
further reduce the requirement of human expertise, such
13
as involving the angles of beams [64] and the numbers
of apertures in the decision variables [11].
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Ye Tian received the B.Sc., M.Sc., and Ph.D.
degrees from Anhui University, Hefei, China,
in 2012, 2015, and 2018, respectively.
He is currently an Associate Professor with
the Institutes of Physical Science and Infor-
mation Technology, Anhui University, Hefei,
China. His current research interests include
evolutionary computation and its applications.
He is the recipient of the 2018 and 2021
IEEE Transactions on Evolutionary Computa-
tion Outstanding Paper Award, the 2020 IEEE
Computational Intelligence Magazine Outstanding Paper Award, and
the 2022 IEEE Computational Intelligence Society Outstanding PhD
Dissertation Award.
Yuandong Feng received the B.Sc. degree from
Hunan Normal University, Changsha, China,
in 2018, where he is currently pursuing the
M.Sc. degree with the School of Computer Sci-
ence and Technology, Anhui University, Hefei,
China.
His current research interests include large
scale multi-objective optimization and its appli-
cations.
Chao Wang received the B.Sc. degree from
Suihua College, Suihua, China, in 2012, and the
M.Sc. and Ph.D. degrees from Harbin Engineer-
ing University, Harbin, China, in 2015 and 2018,
respectively.
He is currently a Lecturer with the School of
Artificial Intelligence, Anhui University, Hefei,
China. His main research interests include evo-
lutionary computation, combinatorial optimiza-
tion, and intelligent transportation.
Ruifen Cao received the B.Sc. degree from
Henan University in 2004, and the Ph.D. de-
gree from Hefei Institutes of Physical Science,
Chinese Academy of Sciences, Hefei, China, in
2010.
From 2010 to 2015, she was a Research Assis-
tant and Associate Researcher with the infor-
mation science and technology. Since 2019, she
has been an Associate Professor with the School
of Computer Science and Technology, Anhui
University. Her current research interest focuses
on medical image processing, artificial intelligence and its application
in radiotherapy.
View publication stats
15
Xingyi Zhang (SM’18) received the B.Sc. degree
from Fuyang Normal College, Fuyang, China,
in 2003, and the M.Sc. and Ph.D. degrees from
Huazhong University of Science and Technol-
ogy, Wuhan, China, in 2006 and 2009, respec-
tively.
He is currently a Professor with the School
of Artificial Intelligence, Anhui University,
Hefei, China. His current research interests in-
clude unconventional models and algorithms of
computation, evolutionary multi-objective op-
timization, and logistic scheduling. He is the recipient of the 2018
and 2021 IEEE Transactions on Evolutionary Computation Outstanding
Paper Award and the 2020 IEEE Computational Intelligence Magazine
Outstanding Paper Award.
Xi Pei received the B.Sc. degree from Nan-
jing University of Aeronautics and Astronau-
tics, Nanjing, China, in 2006, and the Ph.D.
degrees from University of Chinese Academy
of Sciences, Hefei, China, in 2012.
He is currently an Associate Professor with
the School of Nuclear Science and Technol-
ogy, University of Science and Technology of
China, Hefei, China. His main research interests
include key technologies of radiotherapy and
their applications.
Kay Chen Tan (SM’08-F’14) received the B.Eng.
(First Class Hons.) degree in electronics and
electrical engineering and the Ph.D. degree
from the University of Glasgow, Glasgow, U.K.
He is currently a Chair Professor of the Depart-
ment of Computing at the Hong Kong Poly-
technic University, Hong Kong. He has pub-
lished over 200 journal papers and six books,
and holds one U.S. patent on surface defect
detection.
Prof. Tan is currently the Vice-President (Pub-
lications) of IEEE Computational Intelligence Society, USA. He has
served as the Editor-in-Chief of IEEE Transactions on Evolutionary
Computation from 2015-2020 and IEEE Computational Intelligence
Magazine from 2010-2013, and currently serves as the Editorial Board
Member of over 10 journals. He was an IEEE Distinguished Lecturer
Program (DLP) speaker and currently serves as the Chief Co-Editor of
Springer Book Series on Machine Learning: Foundations, Methodolo-
gies, and Applications.
Yaochu Jin (SM’02-F’16) received the B.Sc.,
M.Sc., and Ph.D. degrees from Zhejiang Univer-
sity, Hangzhou, China, in 1988, 1991, and 1996,
respectively, and the Dr.-Ing. degree from Ruhr
University Bochum, Germany, in 2001.
He is an Alexander von Humboldt Profes-
sor for Artificial Intelligence, Chair of Nature
Inspired Computing and Engineering, Faculty
of Technology, Bielefeld University, Germany.
He is also a Distinguished Chair, Professor
in Computational Intelligence, Department of
Computer Science, University of Surrey, Guildford, U.K. He was a
“Finland Distinguished Professor” of University of Jyväskylä, Fin-
land, “Changjiang Distinguished Visiting Professor”, Northeastern
University, China, and “Distinguished Visiting Scholar”, University
of Technology Sydney, Australia. His main research interests include
evolutionary optimization, evolutionary learning, trustworthy machine
learning, and evolutionary developmental systems.
Prof. Jin is presently the Editor-in-Chief of Complex & Intelligent
Systems. He was the Editor-in-Chief of the IEEE TRANSACTIONS
ON COGNITIVE AND DEVELOPMENTAL SYSTEMS in 2016-2021
and an IEEE Distinguished Lecturer in 2013–2015 and 2017–2019, the
Vice President for Technical Activities of the IEEE Computational
Intelligence Society (2015–2016). He is the recipient of the 2018 and 2021
IEEE Transactions on Evolutionary Computation Outstanding Paper
Award, and the 2015, 2017, and 2020 IEEE Computational Intelligence
Magazine Outstanding Paper Award. He was named by the Web of
Science as a Highly Cited Researcher from 2019 to 2021 consecutively.
He is a Member of Academia Europaea.