Introduction
The most common cancer in women and the main
cause of cancer death in women is breast cancer.[] In
several randomized clinical trials, it has been shown that adding chest wall and regional lymph node irradiation
after modified radical mastectomy improves
disease-free survival (DFS) and overall survival (OS)
in breast cancer patients with positive axillary lymph
nodes.[-] Since 1990, the death rate from breast cancer has decreased in industrialized nations due to
better detection methods and a combination of radiation,
chemotherapy, and surgery.[,] Radiotherapy
(RT) is a crucial adjuvant therapy for patients undergoing
breast-conserving surgery or with a high risk
of recurrence after a modified radical mastectomy.
Numerous radiation theories and mechanisms have
evolved throughout time. Tangential opposing fields
with hard wedge filters are used in static three-dimensional
radiotherapy in conventional radiation therapy
(3D-CRT). To give more uniform and conformal dose
distributions for the target volume (PTV), two modern
dynamic irradiation techniques, volumetric modulated
arc therapy (VMAT) and intensity-modulated radiation
therapy (IMRT) have been developed.[-] IMRT
has outperformed three-dimensional conformal radiation
therapy in several locations, including the head
and neck, central nervous system, lung, and prostate
(3DCRT). Using multileaf collimators, IMRT regulates
fluence and breaks a beam into tiny beamlets to provide
the best radiation to the target while preserving vital
organs. In the event of chest wall radiation, the lungs
and heart remain the two most important vital organs.
With high accuracy, IMRT concentrates radiation
on the breast tumor and modifies the radiation beams"
intensities, sparing the surrounding healthy tissue. With
IMRT, each radiation dosage may be precisely adapted
to the breast tumor"s geometrical form.[] On the other
hand, because of increased low-dose exposure and more
monitor units (MU), dynamic radiation techniques
may promote the development of secondary tumors.
[] To maximize the advantages of static and dynamic
radiation treatments, Mayo et al.[] suggested a composite
technique combining 3DCRT and IMRT, dubbed
hybrid IMRT (H-IMRT). Traditional open fields and
IMRT fields computed through inverse treatment planning
optimization are combined in a hybrid IMRT. Our
previous research demonstrated that the hybrid IMRT
plan provided equivalent target coverage and minimal
dosage to neighboring OARs.[] The enhanced dosimetric
potential of flattening filter free (FFF) beams
has been the subject of several articles.[,] Reports
on the impact of the FFF beam on breast radiation may
be found in many articles.[-] Published results
[,-] show that 3DCRT is a good base-dose plan
for breast RT ideas that use a flat beam of photons.
The current research uses the 3DCRT with the FF
photon beam as the base plan and incorporates the FFF
photon beam into the hybrid IMRT treatment plan.
This research aims to evaluate the hybrid IMRT treatment
plan using FF and FFF photon beams. In addition, a novel idea known as the Unified Dosimetry Index
(UDI) was put forth by Akpati et al.[]. The UDI,
used to rank the designs, was used to assess the plans
using different dosimetric indices. Full uniform dose
coverage, flawless target fit, and a gradual fall-off dosage
beyond the target are all characteristics of a great
plan.[-] The four dosimetric indicators, coverage
index (C), conformity index (CI), homogeneity index
(HI), and gradient index (GI), as well as the UDI rating,
are all taken into account. It was recommended to
have the lowest possible UDI score.
Methods
Patient Simulation and Target Delineation
Fifteen female patients with infiltrating ductal carcinoma
of the left breast were chosen for this study. Their
primary diagnosis was left breast cancer with lymph
nodes in the supraclavicular and axillary regions (SCL).
All patients were treated for 15 fractions with a Field-in-
Field (FiF) treatment plan with a daily dose of 2.67 Gy.
All patients were immobilized in the head first supine
position and scanned in a Siemens CT Scanner
with a 3 mm slice thickness. A Carbon Fiber breast
board was used to immobilize the patients, and their
left arms were lifted above their heads to keep them out
of the treatment field. After the planning CT was finished,
digital imaging and communication in medicine
(DICOM) pictures were uploaded to the Eclipse treatment
planning system (version 16.1, Varian Medical
Systems, USA). The body outlines the ipsilateral lung
(IL), contralateral lung, contralateral breast, heart, spinal
cord, and planning target volume (PTV), as well as
the gross tumor volume (GTV), clinical tumor volume
(CTV), and PTV, were developed. The GTV, or GTV, is
the total lumpectomy cavity that can be detected using
surgical clips implanted after surgery. The CTV, PTV,
and organs at risk (OARs) were created using the RTOG
protocol. The CTV was defined by a three-dimensional
uniform 1.5 cm margin expanded in all directions surrounding
the GTV. However, it had to fit within 5 mm
of the external contour and up against the main muscle.
Treatment Planning
Eclipse treatment planning system (TPS) V16.1 (Varian
Medical Systems, USA) was used to generate the
hybrid plan for vital beam linear accelerator (LINAC)
equipped with 120 micro leaf controllers (MLC). For
each patient, hybrid IMRT plan with 6MV FF photon
beam (hybrid-FF) and FFF photon beam (hybrid-FFF)
were created. Both the Hybrid plans are optimized by keeping the 3DCRT treatment plan as a base. Please
put the photograph of all the plans described in this
paper. The 3DCRT plan had two coplanar open tangential
fields that passed via an isocenters axially at the
lung-PTV interface and craniocaudally at the center of
the PTV (photograph, please). With collimator angles
of 0°, the gantry angles were calculated based on the
PTV curvature, heart, and IL involvement. These tangential
fields were extended 2.5 cm outside the body
to account for the breast setup mistake. The analytical
anisotropic algorithm (AAA) was used for volume
dose calculation using a 2.5 mm dose grid matrix. All
3DCRT plans were normalized to deliver prescription
doses to PTV mean. Two 3D-CRT and 2 IMRT
beams are combined in hybrid IMRT planning. Plans
for hybrid IMRT were created in two steps. Two tangent
open beams of 6 MV photon beam is used to conform
the breast PTV make up step one. With a 60%
beam weightage, doses were computed for the tangent
fields. The 3DCRT plan was used as the base plan while
optimizing an IMRT treatment plan with 6 MV Photon
beam with a similar beam angle. The fluence was
computed for the IMRT field. Step 2 involved copying
the 3DCRT beam to the IMRT plan and calculating
the final dose along with 2 open tangent field calculated
in step 1. A hybrid plan consists of 3DCRT and
IMRT plan in a 60:40 ratio. All plans were normalized
to achieve mean PTV doses equal to prescribed dose.
Similar methodology was involved in the development
of hybrid IMRT plan with FFF photon beam. Hybrid-
6FF and hybrid 6FFF treatment plan is developed with
6 MV FF and 6MV FFF photon beam, respectively.
Hybrid 6FFF treatment plan consists of 3DCRT plan
with 6MV FF photon beam and IMRT plan with 6MV
FFF photon beam. Photon optimizer (PO) was used for inverse treatment plan optimization. A leaf motion
calculator was used to convert the fluences into
dynamic MLC sequences, and final dose computation
was performed with the AAA algorithm. During Inverse
optimization, dose constraints listed in Table 1
were utilized. Both hybrid IMRT plan uses the same
optimization parameter and dose penalty.
Table 1 Treatment planning objective and dose constraints
Planning Evaluation Indices
The treatment plans can be evaluated qualitatively by
performing a visual slice-by-slice examination using
isodose line distribution. A qualitative assessment is
required for treatment plans containing hot and cold
areas. Dose volume histograms (DVH) were all included
in the quantitative analysis. To assess the dose
to various structures in various schemes, DVH was
developed. The dose-volume parameters D98% (minimum
dose received by 98% of PTV volume) and D2%
(maximum dose received by 2% of PTV volume) were
analyzed for PTV as per the International Commission
on Radiation Units and Measurements (ICRU) report
83.[26] DVHs were used to calculate various dosimetric
indices doses for PTV and OARs and to compute
the integral doses for the OARs.
Statistical Tools and Analysis
The statistical analysis was conducted using IBM Corporation's
Statistical Software Package for the Social Sciences
(SPSS) version 17.0. To find the mean and median,
descriptive analysis was used. To compare the Hybrid FF
plan to the Hybrid FFF plan IMRT, a paired t-test was
used. For statistical significance, p=0.05 was used. 100%
of the PTV receiving the prescribed dose is referred to as
dose coverage. It is a metric that indicates how effectively
the prescribed dose covers the PTV. It is acceptable
to have a plan that covers 92% of the required dose.[]
Coverage index (C)=PTVPI/PTV
Where PTVPI is the PTV getting the prescribed
isodose (PI), as stated in ICRU Report No. 62,[]
RTOG recommended the CI in 1993. The relationship
between the volumes of the reference dosage and the
target dose is displayed.
Conformity index (CI)=VIR/TV
Where VIR is the reference dose volume, and TV is
the total target volume.
To assess the level of conformity, CI value ranges
have been defined. The ideal CI value is 1, according
to the theory. The treatment is deemed to comply with
the treatment plan if the CI is between 1 and 2. RTOG
proposed guidelines for routinely evaluating plans on
several factors and HI in 1993. The dosimetric analysis
of the treatment plan served as the foundation for developing
the HI concept.[]
Homogeneity Index (HI)=Imax/RI
Imax is the target's maximal isodose, and RI is the reference
isodose.
If HI value is 0
2
HI ≥2.5: Major violation.
The dose GI can compare plans that are similar in
conformance but have distinct dose gradients. GI evaluates
the quality of this dose gradient. The dose GI can
compare plans that are similar in conformance but have distinct dose gradients. The ratio of the volume receiving
the PI line to the volume receiving half of the recommended
isodose line is known as the dose GI.[]
Dose gradient index (GI) =D50%/D100%
Where D100%: Volume of the prescribed dose.
D50%: Volume of half the prescribed dose.
All four parameters stated above are included in
the UDI. It is an effective tool for determining the best
treatment plan strategy. The CI, HI, GI, and C are the
ideal parameter to evaluate treatment plan quality.
Changes can influence UDI's value in any of the four
components. A UDI value near 1 is preferable, while a
greater UDI value is not considered.
UDI=CN×CI×HI×GI
Results
Table 2 summarizes the patient"s characteristics. The
patient's age ranged from 31 to 65 years, with a mean
of 50±10.56 years. The average PTV volume was
313.15 cc with a standard deviation of 105.81 cc. The
PTV volume ranged from 109.1 cc to 530.9 cc. Right,
and left lung volumes were 827.19±153.50 cc and
945.91±143.39 cc, respectively. The heart and contralateral
(C/L) breast volumes were 502.67±133.91
cc and 790.07±310.68 cc, respectively.
Table 2 Patient demographic, tumour staging, PTV and OARs Volume characteristics
Table 3 shows the different treatment plan quality
index comparisons for 6FF_Hybrid and 6FFF_Hybrid
treatment plans. The coverage index for the 6FF_Hybrid
plan was 0.945±0.013, and for the 6FF_Hybrid
treatment was 0.950±0.007 with p>0.05. PTV
in the 6FF hybrid plan had a conformity index of
0.970±0.010, whereas the 6FFF Hybrid had a conformity
index of 0.963±0.021 with p>0.05. The hybrid IMRT
treatment with 6FF and 6FFF photon beams had HI values of 1.125±0.026 and 1.134±0.025, respectively. In
the 6FF_Hybrid and 6FFF_Hybrid treatment plans, an
insignificant GI value of 1.050±0.020 and 1.042±0.017
was found (p>0.05). A UDI scoring of 1.090±0.023 and
1.078±0.024 was observed between 6FF_Hybrid and
6FFF_Hybrid treatment plans with p>0.05.
Table 3 Illustrates the dosimetric parameter for the planning target volume (PTV) in the intensity modulated radiation
therapy (IMRT) plan for 6X_FF (Flattened Filter) & 6X_FFF (Flattened Filter Free)
Table 4 illustrates the different volumetric doses to the
OARs for the 6FF-Hybrid and 6FFF_Hybrid IMRT plans.
V5Gy and V10Gy of the IL were smaller in the 6FF_Hybrid IMRT plan compared to the 6FF_Hybrid IMRT plan
(p>0.05). V20Gy of IL received a lesser dose in 6FF_Hybrid
than 6FFF_hybrid IMRT plan (p>0.05). The mean dose
of the IL was less in the 6FF_Hybrid IMRT plan than in
the 6FFF_Hybrid plan (p>0.05). V20Gy and V10Gy of the
heart were reported with smaller radiation doses in the
6FF_Hybrid IMRT plan compared to the 6FFF_Hybrid
IMRT treatment plan (p>0.05). Significantly, the 6FFF_
Hybrid IMRT plan delivers lower doses of radiation in
comparison to the 6FF_Hybrid IMRT plan. The Dmax of
the contralateral breast significantly received reduced
doses of radiation on the 6FFF_hyrid plan concerning
the 6FF_Hybrid plan. D5% of contralateral breasts receives
an insignificantly lesser dose in 6FFF_Hybrid
IMRT compared to 6FF_Hybrid plan.
Table 4 Illustrate the dosimetric indices for the Organs at Risk (OARs)
Integral Doses
Table 5 shows the comparison of integral dose (ID), monitor
unit (MU), and beam on time (BOT) between the
6FF_Hybrid IMRT and 6FFF_Hybrid IMRT. ID for I/L
lung was 6387±1658.51 (Gy-L) and 6347.056±1643.41
(Gy-L) in 6FF_Hybrid and 6FFF_Hybrid IMRT plan
(p<0.05), respectively. I/p breast was reported with ID
of 117.27±30.819 (Gy-L) and 101.61±27.07 (Gy-L) in
6FF_Hybrid and 6FFF_Hybrid IMRT plan (p<0.05).
ID value to heart was 2272.52±1086.63 (Gy-L) and
2212.40±1059.49 (Gy-L) in 6FF_Hybrid and 6FFF_
Hybrid IMRT plans (p>0.05), respectively. The number
of MUs for the 6FF_Hybrid and 6FFF_Hybrid IMRT
plans was 529.14, 50.46 and 761.07 102.51, respectively,
with a significant difference of p<0.05.
Table 5 Show the Comparison of ID, MU and BOT between 6FF_Hybrid and 6FFF_Hybrid IMRT Plan.
The BOT in the 6FF_Hybrid IMRT plan was
much lower than in the 6FF_Hybrid IMRT plan.
6FF_Hybrid and 6FFF_Hybrid IMRT plans have
BOT values of 0.882±0.08 and 0.5436±0.07, respectively
(p<0.05).
Discussion
A limited study is available for a Hybrid treatment
plan compared with IMRT, 3DCRT and VMAT.
[,] Numerous studies have compared the IMRT
treatment with the FFF photon beam and FF photon
beam for the different treatment sites. They have
concluded that no significant dose difference was observed
between the IMRT treatment plan with FF and
FFF photon beam. Figure 1 shows the color dose wash
of 95% isodose of prescribed dose for 6FFF and 6FF
Hybrid IMRT treatment plan.
Fig. 1. The color dose wash of 95% of dose distribution of prescribed dose for 6FFF and 6FF Hybrid IMRT plan.
FF: Flattened Filter; FFF: Flattened Filter Free; IMRT: Intensity-modulated radiation therapy.
Figure 2a shows the CI, C, and HI comparison between
the FF and FFF Hybrid treatment plans. Similar
results were also observed in our study of Hybrid
treatment plans with and without the flattening filter.
No significant dose difference was found for PTV
target coverage (C, CI, and HI between 6FF_Hybrid
IMRT and 6FFF_Hybrid IMRT treatment plan. Figure
2b compares GI and UDI between the FF and
FFF Hybrid plans. Higher dose fall is one of the main
characteristics of the FFF photon beam, but here in
our study, the GI value for a hybrid plan using the
FFF photon beam does show how significant the difference is from that of the FF hybrid plan. Comparing
the UDI score, the FFF hybrid plan has a lesser score
than the FF hybrid plan. One of the dominating factors
in calculating UDI was the GI value.
Fig. 2. (a) The comparison of various treatment plan quality Indices and (b) comparison
of gradient index and unique dosimetric index between the 6FF_Hybrid and 6FFF_
Hybrid treatment plans.
FF: Flattened Filter; FFF: Flattened Filter Free; HI: Homogeneity index.
The fundamental goal of the hybrid technique is
to preserve the heart, I/L, C/L lung, and C/L breast to avoid radiation-induced secondary cancers and
long-term consequences (such as heart failure and
lung pneumonia).
Figure 3 illustrates the volume of the left lung receiving
various doses in the 6FF_hybrid and 6FFF_Hybrid
treatment plan. Radiation pneumonitis, which subsequently develops into irradiated lung fibrosis, can
affect patient's right after irradiation. Clinically severe
pneumonitis should be uncommon in breast cancer patients
if the V20Gy of the IL is <30%. V20Gy was the lowest
in both types of Hybrid plans and achieved the lowest
value in the FFF hybrid plan. V5Gy and V10Gy were well
below their threshold value, and FFF hybrid attains the
lowest volume compared to the FF Hybrid plan.
Fig. 3. The doses to the left lung in 6FF_Hybrid and 6FFF_Hybrid treatment plan. V20Gy
(%): Volume of 20Gy received in % by specific organ.
FF: Flattened Filter; FFF: Flattened Filter Free; Gy: Gray; Vxx: Volume received by xx dose in Gy.
Another important OARs while treating the cabreast
with radiation therapy is the heart. The Figure
4 shows the comparison of mean dose, V20Gy and V10Gy received by heart between 6FF_hybrid and 6FFF_Hybrid
treatment plan. Evidence from various research
indicates that for every additional 1 Gy given to the
heart's normal exposure, the incidence of major coronary
accidents rises by 7.4%.[32] The average Dmean
to heart was 2.6% lower in the FFF Hybrid plan than
in the FF hybrid. Our study achieved the mean dose
to heart well below the planning threshold in both
planning schemes.
Fig. 4. The comparison of heart doses between the 6FF_Hybrid and 6FFF_Hybrid Treatment
plans.
FF: Flattened Filter; FFF: Flattened Filter Free; Gy: Gray.
ID is the absorbed dose within the specific organ.
The distribution of the ID doses for the heart and lungs for the 6FF_ and 6FFF_ Hybrid IMRT Treatment
Plans is shown in Figure 5. It is typically reported
that the ID of IMRT increases as the number
of small aperture and monitor units increases.
6FFF_Hybrid plan has more MU than the 6FF_Hybrid
plan, but the ID for the heart and left lung was
less in the 6FFF_Hybrid plan than the 6FF_Hybrid
plan. This could be because of the less scattered dose
in the FFF photon beam. Saroj et al.[] reported
similar results. 70% reduction in scattered dose for
IMRT planning with FFF photon beam is reported
by Cashmore et al.[]. Another advantageous aspect
of the FFF photon beam is the availability of a higher
dose rate. IMRT plan with FFF photon beam has
more MU than FF IMRT plan. Our finding is consistent
with the literature. We have seen a 44% increase
in the number of MUs with the 6FFF_Hybrid IMRT
plan as opposed to the 6FF_Hybrid IMRT plan. FFF
photon beam with a high dose rate will help deliver
the higher MU in a shorter time. A 62% reduction
is observed in BOT for the 6FFF_Hybrid plan compared
to 6FF_hybrid Plan. Lower BOT will help reduce
patients" couch time during treatment.
Fig. 5. The integral dose comparison between 6FF_Hybrid and 6FFF_Hybrid treatment
plans for the heart and left lung.
FF: Flattened Filter; FFF: Flattened Filter Free; ID: Integral dose; Gy: Gray, L: Liter.
Conclusion
The scope of the hybrid treatment plan was expanded
with additional benefits by including the FFF photon
beam. The FFF photon beam hybrid technique still
provides a desirable and acceptable treatment plan. A
hybrid IMRT treatment plan with FFF photon beam
characteristics spares the OARs better than a hybrid
IMRT plan with an FF photon beam, giving patients a
higher standard of living. Finally, our study concludes
that using an FFF photon beam in a Hybrid IMRT
plan for the ca-breast patient will be beneficial due
to better OARs sparing, less scattered dose, and faster
treatment delivery.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Financial Support: None declared.
Authorship contributions: Concept - S.H., A.D., B.S.;
Design - S.H., B.S., A.D.; Supervision - A.D., B.S.; Data collection
and/or processing - S.H., A.D., B.S.; Data analysis
and/or interpretation - S.H., B.S., A.D.; Literature search
- S.H., A.D., B.S.; Writing - S.H., B.S., A.D.; Critical review
- B.S., A.D., S.H.
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