Introduction
Till date, cancer is among the most feared diseases
with high mortality rate. Consistence with this, an estimated
number of new cancers were diagnosed in 2019
in the United State as 1.762.450, with a total of 606.880 deaths recorded.[] In Nigeria, according to the International
Agency on Research on Cancer, as of 2018,
the total number of new cases was 115.950, with 70.327
deaths recorded.[] Prostate cancer is the second leading
cause of cancer in men. In 2019, a total of 174.650
men were diagnosed with prostate cancer in the United States (cancer.net) and, in Nigeria, an estimated hospital
prevalence of between 127 and 185.5 per 100.000
males admitted in hospitals were diagnosed of prostate
cancer.[] Prostate cancer can be treated by surgery, radiation
therapy, chemotherapy, cryotherapy, hormone
therapy and immunotherapy, and newer technological
development.[] Radiation therapy has a dynamic role
in the treatment of prostate cancer. It involves the use
of various treatment plans (TPs) such as 2D- technique,
3D-Conformal Radiation Therapy (3D-CRT), and intensity
modulated radiotherapy (IMRT). 2D- technique
involves manual calculations and does not spare organs
at risk (OAR). 3D-Conformal Radiation Therapy (3DCRT)
is a conformal TP that conforms the radiation
doses to the target and, in history, was the best TP for
prostate cancer, but results to little sparing of OAR. With
intensity modulated radiotherapy (IMRT), the reduction
of radiation effect on normal tissues has improved. Research
has shown that IMRT has more advantages compared
to 3D-CRT in the treatment of prostate cancer. In
this study, we investigated the use of homogeneity index
(HI) and conformity index (CI) in the evaluation of 3DCRT
and IMRT plans for optimal treatment delivery.
Methods
Patients Selection
Ten patients with malignant neoplasm of prostate that
received radiotherapy with IMRT on a clinical linear
accelerator (LINAC), Vitalbeam model (Varian Medical
System, Palo Alto, CA, USA) in our department
from June 2019 to January 2020 were analyzed, retrospectively.
Simulation and Contouring
Each patient was asked to stay on a supine position on
a whole-body board (Radon Medical Equipment, Yenimahalle/
ANKARA) without immobilization and was
simulated with a 16-slice computed tomography (CT)
simulator (Optima 580; GE Healthcare, Waukesha,
WI, USA). The plans were sequentially done in three
phases. The clinical treatment volume (CTV) for one of
the cases was contoured in two phases and nine cases
were contoured in three phases. Each planning target
volume (PTV) was contoured with 0.5 cm margin from
each CTV. Phase 1 (PH 1) contains the prostate, seminal
vesicle, and lymph node. Phase 2 (PH 2) contains
the prostate and seminal vesicle only, while phase 3
(PH 3) contains the prostate only. However, the case
with two phases had phase 1 (the prostate+seminal
vesicle+lymph node) and phase 2 (the prostate only) (Table 1). The OARs, which are rectum, bladder, and
femoral heads (left and right), were also contoured
according to the Radiation Therapy Oncology Group
(RTOG) atlas for contouring of normal tissue [5] using
the Eclipse TP system version 15.6.
Table 1: Showing the prescribed doses for the ten patients
for both 3D-CRT and IMRT
TPs
Two plans were generated for each patient using
the Eclipse TP system version 15.6, with energy of 6
MV photons. The prescribed dose was as follows: 76
Gy for three cases; 79 Gy for six cases; and 69 Gy for
the patient planned in two phases as shown in Table
1. The different prescription was due to the different
non-use of uniform prescription model in our center.
The oncologist's prescription type depended on the
cancer stage. Each 3D-CRT plan was produced using
four beams (box technique) at the gantry angles of 0°,
90°, 180°, and 270°. Multi-leaf collimators (MLC 120
model) were used at 0.5 cm away from PTV to reduce
dose to OAR and for more conformity of the 3D-CRT
plans. The IMRT plans were done using five beams at
the gantry angles of 0°, 72°, 144°, 216°, and 288°. The
intensity optimization for each of the beam portals for
all IMRT plans was achieved by setting dose constraints
and priorities for PTV and OAR until the constraints
were met, following the International Commission on
Radiation Units and Measurement (ICRU) protocol
for dose prescription, with a minimum coverage dose
of 95% and maximum accepted dose of 107%.[6] The
doses were calculated using Anisotropic Analyses Algorithm
in the Eclipse TP system, with the treatment
table or couch not included in the calculation volume.
When creating the IMRT plan for a LINAC equipped
with an MLC, there were two delivery options: stepand-
shoot and sliding window. For this study, the sliding
window was adopted for all the IMRT plans.
The Quantitative Analysis of Normal Tissue Effects
in the Clinic (QUANTEC) analysis and Radiation
Therapy Oncology Group (RTOG) Report 62 (a review
of Report 50) guideline were adopted for the dose constraint
reaching the OAR. The guideline stipulates that not more than 35% of the rectum should receive 60 Gy
(V60 Gy <35%) and not more than 20% of the rectum
should receive 70 Gy (V70 Gy <20%). Also, for the
bladder, not more than 15% of the bladder should receive
80 Gy (V80 Gy <15%), not more than 25% should
receive 75 Gy (V75 Gy <25%), not more than 35%
should receive 70 Gy (V70 Gy <35%), and not more
than 50% should receive 60 Gy (V60 Gy <50%). For the
femoral heads, not more than 5% of the femoral heads
should receive 50 Gy (V50 Gy <5%).[5,7-9]
Dose Volume Analysis
The plan sums for the different plans were generated
and data were collected from their dose volume histogram
(DVH). From the DVH, the value of dose in Gy
reaching the following volume of PTV was recorded:
V2%, V5%, V50%, V95%, and V98%. Also, the maximum
isodose in the target (Imax) and the reference
isodose reaching V95% of PTV were also recorded.
CI and HI
CI and HI were calculated and recorded for each TP
using the following equations:[10,11]
Where VRI is volume of the target receiving 95% of the
prescribed dose and TV is the total volume of the target.
Where Imax is maximum dose in the target RI is reference
isodose and
D≥95% is dose at 95% of planning target volume
D≥5% is dose at 5% of PTV
Using the calculated conformity and homogeneity indices
according the RTOG protocol, we evaluated the
TP that conforms more to PTV and is more homogeneous.
The RTOG protocol defines the range of conformity
and homogeneity as follows:
• If CI value is between 1 and 2; then, the treatment is
in accordance with the protocol.
• If CI value is between 2 to 2.5 and 0.9 to 1; then,
there is a minor deviation of the protocol.
• If the CI value is >2.5 and <0.9, it is considered as a
severe deviation from the protocol.
For homogeneity, the ideal value for HI is 1 and it increases
as the plan becomes less homogeneous. Values
closer to 1 are more homogeneous than values away
from 1. The mean doses reaching the rectum, bladder,
Right, and left femoral heads were also analyzed for
each plan.
Statistical Analysis
A two-tailed pair t-test was used to compare the mean
of the different TPs at critical significant value of 5%.
Results
In this study, the dose distribution for IMRT plan is
more aligned to PTV than that of 3D CRT plan (as
shown in Figure 1), which, in turn, reduces the dose
to OAR. The dose coverage for both 3D-CRT and the
IMRT TPs met the required criteria of at least 95%
of the prescribed dose of PTV. The dose maximum
was in the range of 105.5%?108% for 3D-CRT plans, although it was one of the plans that had up to 108%,
which was due to the large size of the PTV. However,
the dose maximum for IMRT was in the range of
104.5%-106.7%.
Fig 1: Showing the dose distribution of a 3D-CRT and IMRT plans for a selected patient.
Figure 2 shows the DVH of patients planned with
3D-CRT (left) and IMRT (right) treatment techniques,
comparing their PTVs. The square box shows the PTV
coverage of the TP done using IMRT technique, while
the triangular shape is the PTV coverage of the TP
done using 3D-CRT TP technique.
Fig 2: Comprasion between the PTV coverage of the plan sum of 3D-CRT and IMRT plan.
HI
Results from the HI, H1, for the ten patients planned
with 3D-CRT were in the range of 1.069-1.170, with an
average of 1.088±0.03. For IMRT, HI were in the range
of 1.056-1.102, with an average of 1.072±0.002. Also,
HI (H2) for 3D-CRT were in the range of 1.029?1.128,
with an average of 1.062±0.04. However, for IMRT, HI (H2) were in the range of 1.021?1.069, with an average
of 1.044±0.02.
CI
The CI for each TP was calculated using equation 1.
Figure 2 shows the dose coverage from the DVH. Table
2 shows the comparison between the CI of 3D-CRT
and IMRT.
Table 2: Comparison between the Organ at Risk for 3D-CRT and IMRT plans. V20 (Gy) and V50 (Gy) represents the dose to
20% volume and 50 % volume of the OAR respectively. (QUANTEC)
OAR
The dose to OAR of each patient planned using 3DCRT
was compared to that of IMRT, as shown in the
DVH in Figure 3. The DVH shows the dose to the
rectum (brown), bladder (purple), left femoral head
(blue), and right femoral head (sky-blue) for both TP.
Tables 2 shows the mean results of dose to OAR for
3D-CRT and IMRT.
Fig 3: DVH of OAR for 3D-CRT and IMRT treatment planning tecniques for one patient.
Discussion
In the treatment of cancer, sparing of OAR is one of
the goals of radiotherapy. This was considered in this
study. Both techniques were evaluated for sparing of
OAR using the plan sum of the three phases. This study
was aimed at comparing 3D-CRT and IMRT TPs in
the treatment of neoplasm of prostate by comparing
their HI, CI, and dose to OAR. The results from this
study (Tables 2) show that IMRT is much better than
3D-CRT in terms of sparing of OAR. For 3D-CRT, it
was observed that it was difficult to meet the RTOG
dose constraint protocol for rectum, since the dose
reaching 50% volume of the rectum was more than 50
Gy in most cases (Table 2); however, most of the plans
met the QUANTEC protocol of 20% of the volume receiving
70 Gy (Table 2). For IMRT, the dose to OAR
was within the tolerance set by RTOG and QUANTEC
(Tables 2).
Table 2 shows the comparison between the OAR
of 3D-CRT and that of IMRT. V20 (Gy) and V50 (Gy)
represents the dose to 20% and 50% volume of OAR,
respectively (QUANTEC). There was 21% reduction in
dose to 20% volume of the rectum in IMRT and 27%
reduction in dose to the 50% volume of the rectum in
IMRT relative to the 3D-CRT plans. 20% reduction in
dose to 20% volume of the bladder and 40% reduction
in 50% volume of the bladder in IMRT was also
observed. More also, in the 20% volume of the right
femoral head, there was 7.2% reduction and 42% reduction
in the 50% volume of the right femoral head in
the IMRT plans. The 20% of the left femoral head experienced a 27% reduction in dose and 39% reduction
in 50% volume of the dose received in the left femoral.
These results were not comparable with other works
because other studies evaluated different parameters.
Although several studies evaluated 3D-CRT and
IMRT plans for single phase, this study paid more
attention to plans of three phases and evaluation was
done using their plan sum. More also, studies evaluating
one and two phases were compared with our
results. These studies adopted the HI defined by Wu
et al.[] In this study, the HI adopted was defined by
RTOG protocol (defined as H1) and Yoon et al., (defined
as H2), as stated in the materials and methods,
and were compared using similar standard. From the
result of this study (Table 3), HI (H1) for IMRT showed
a better homogeneity when compared to that of 3DCRT
(p-value=0.03). This result was close to that of H2
(Table 3); however, there was no statistically significant
difference between the two techniques (p-value=0.16).
By relating the two results got from both protocols, it
was discovered that the HI formula defined by Yoon
et al., was closer to 1 than the RTOG protocol, since
HI closer to 1 is the baseline for good homogeneity according
to both protocols. Also, in this study, the result
of CI (Table 3) shows that the conformity of IMRT
(0.99) was better than that of 3D-CRT plans (0.91),
such that it had a conformity closer to 1 than that of
3D-CRT. There was a statistically significant difference
between the mean of both plans (p-value=0.23).
Compared to the study of Crowe et al.,[] this CI of
this study was closer to 1 when using the RTOG protocol.
This was consistent with the study by Cristofaro et al.[] and Jamal, et al.[] The result from this study
contradicts that of Kinhkikar, et al.,[] since their CIs
were 0.97±0.02 and 0.98±0.02 for IMRT and 3D-CRT,
respectively, thus resulting in a better conformity in
3D-CRT than in IMRT. This may be due to the level of
experience of the IMRT planner.
In this study, the mean dose to the left femoral head
was reduced by 40.2% in IMRT. This was consistent with
the study by Uysal et al.,[] who reported a mean dose
of 18.79±18.79 and 31.5±4.11 Gy for IMRT and 3D-CRT,
respectively, thus resulting in 40.3% reduction. This was
also consistent with the study by Cristofaro, et al., and
Crowe et al. In Table 3, the volume of the bladder receiving
35 Gy (V35) had 20.1% reduction in IMRT and
this result was close to the result of Kinhikar et al., with
23.7% reduction in IMRT for V35. The volume of the bladder receiving 40 Gy had a reduction of 49.9% reduction
in IMRT relative to 3D-CRT. This was higher than
the 41%, 37.61%, 24.7%, and 26.8% reported by Cristofaro,
et al., Ashman et al.,[] Uysal et al., and Kinhikar
et al., respectively. For the rectum, the volume receiving
40 Gy had a 32.7% reduction in IMRT relative to 3DCRT.
Crowe et al., had a reduction of 49% in the volume
receiving 40 Gy in IMRT, while 50% reduction was
reported by Kinhikar et al. However, Cristofaro, et al.,
had 34% reduction, which is closer to our result. Other
studies by Wortel et al.[] and Panayiotis et al.[] also
had reduction in IMRT.
Generally, the results from this study were comparable
to that of other studies; however, homogeneity
and conformity indices were better and had lesser dose
to OAR.
Conclusion
Twenty TPs of 3D-CRT and IMRT were created and
their CI and HI were evaluated for ten prostate patients.
Also, the dose to OAR was evaluated. The use of IMRT
TP technique for prostate cancer proved to be superior
over 3D-CRT and in sparring dose to OAR. More also,
the control of normal tissue complication probability is
better with plans done in more than one phases compared
to those done in a single phase.
Acknowledgement: The authors would like to appreciate
the management of NSIA-LUTH Cancer Care (NLCC) Lagos,
Nigeria for granting us the permission to use the center
for this study.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: This study was approved by
the College of Medicine University of Lagos Ethics Committee
(no. 17758, date: 06/08/2018).
Financial Support: None declared.
Authorship contributions: Concept - S.A., M.A., M.H.,
A.O., A.J.; Design - M.A., A.D., A.O., S.A., M.A.; Supervision
- S.A., M.A., M.A., M.H., J.A.; Funding ? None; Materials
- A.D., M.A.; Data collection and/or processing - J.A.,
A.J., A.O., M.A.; Data analysis and/or interpretation - A.J.,
A.O., S.A., M.A.; Literature search - M.A., A.D.; Writing -
S.A., M.A., M.H., A.O., A.J., J.A., A.D., M.A.; Critical review
- S.A., M.A., M.H., A.O., A.J., J.A., A.D., M.A.
References
American Cancer Society: available at: https://www.
cancer.org/research/cancer-facts-statistics/all-cancerfacts-
figures/cancer-facts-figures-2019.html. Accessed
Jun 8, 2020.
The International Agency for Research on Cancer: The
Global Cancer Observatory. 2019. Available at: https://
gco.iarc.fr/. Accessed Jun 8, 2020.
Nigeria Health Blog. Available at: https://nimedhealth.
com.ng/2019/02/05/prostate-cancer-in-nigeria-epidemiology-
awareness-screening-symptoms-treatment.
Accessed Jun 8, 2020.
Hou H, Swanson D, Barqawi AB. Modalities for Imaging
Prostate Cancer. Hindawi Publishing Corporation
Advances in Urology 2009;65:12.
Quantitative Analysis of Normal Tissue Effects in
Clinic (QUANTEC). International Journal of Radiation
Oncology, Biology and Physics 2010;76(Suppl):
S3?S9.
ICRU. Prescribing, Recording, and Reporting Intensity-
Modulated Photon-Beam Therapy (IMRT)(ICRU
Report 83). Journal of International Commission on
Radiation Units and Measurements 2010;10:1?106.
Viswanathan AN, Yorke ED, Marks LB. Radiation
dose-volume effects of the urinary bladder. International
Journal of Radiation Oncology, Biology and
Physics 2010;76(Suppl. 3):S116-22
Michalski JM, Gay H, Jackson A, Tucker SL, Deasy JO.
Radiation dose-volume effects in radiation-induced
rectal injury. International Journal of Radiation Oncology,
Biology and Physics. 2010;76(3 Suppl):S123-9.
Eifel PJ, Winter K, Morris M, Levenback C, Grigsby
PW, Cooper J, et al. Pelvic irradiation with concurrent
chemotherapy versus pelvic and para-aortic irradiation
for high-risk cervical cancer: an update of radiation
therapy oncology group trial (RTOG) 90-01. J
Clin Oncol 2004;22(5):872?80.
Knoos T, Kristensen I, Nilsson P. Volumetric and dosimetric
evaluation of radiation treatment plans: radiation
conformity index. Journal of Radiation Oncology,
Biology, Physics 1998;42(5):1169?76.
Yoon M, Park SY, Shin D, Lee SB, Pyo HR, Kim DY. A
new homogeneity index based on statistical analysis of
the dose-volume histogram; Journal of Applied Clinical
Medical Physics 2007;8(2):9?17.
Wu VW, Kwong DL, Sham JS. Target dose conformity
in 3-dimensional conformal radiotherapy and intensity
modulated radiotherapy. Radiotherapy Oncology
2004:71(2):201?6.
Crowe SB, Kairn T, Middlebrook N, Hill B, Christie
DR, Knight RT, et al. Retrospective evaluation of
dosimetric quality for prostate carcinomas treated
with 3D conformal, intensity modulated and volumetric
modulated arc radiotherapy. J Med Radiat Sci
2013;60(4):131?8.
Cristofaro N, Hindson B, Sanderson C. Retropective
dosimetric comparison of three-dimensional conformal
radiotherapy (3D-CRT), sliding window intensity
modulated radiotherapy (IMRT) and volumetric modulated
arc therapy (VMAT) for protate cancer. 2014,
R-0144. Available at: https://epos.myesr.org/poster/
ranzcr/ranzcr2014/R-0144. Accessed Jun 8, 2020.
AL-Shareef JM, Attalla EM, Khalil MM, Abdelaal
AM, El-Nagdy MS. A comparison of intensity modulated
and 3-Dimensional conformal radiotherapy for
prostate cancer using 6-MV and 15-MV photon energies.
Arab Journal of Nuclear Science and Applications.
2020;53(2):189?200.
Kinhikar RA, Pawar AB, Mahantshetty U, Murthy V,
Dhehpande DD, Shrivastava SK. Rapid Arc, helical
tomotherapy, sliding window intensity modulated
radiotherapy and three dimensional conformal radiation
for localized prostate cancer: A dosimetric comparison. Journal of Cancer Resaerch and Therapeutics
2014;10(3):575?82.
Uysal B, Beyzadeoglu M, Sager O, Dincoglan F, Demiral
S, Gamsiz H, et al. Dosimetric evaluation of intensity
modulated radiotherapy and 4-Field 3D-confromal
radiotherapy in prostate cancer. Balkan Medical
Journal 2013;30:54?7.
Ashman JB, Zelefsky MJ, Hunt MS, Leibel SA, Fuks
Z. Whole pelvic radiotherapy for prostate cancer using
3D conformal and intensity-modulated radiotherapy;
International Journal of Radiation Oncology Biology Physics 2005;63(3):765?71.
Wortel R, Incrocci L, Pos F, Van Der Heide U, Lebesque
J, Aluwini S, et al. PO-0742: Image-guided IMRT reduces
late toxicity compared to 3D-CRT for prostate
cancer. Radiotherapy and Oncology 2016;119(Supplement
1):S346?S7.
Mavroidis P, Komisopoulos G, Buckey C, Mavroeidi
M, Swanson GP, Baltas D, et al. Radiobiological evaluation
of prostate cancer IMRT and conformal-RT
plans using different treatment protocols. Phys Med
2017;40:33?41.
