Introduction
Breast cancer is the most common malignant tumors
among the women.[] Adjuvant radiotherapy (RT) is
one of the standard treatments in particular cases and
decreases locoregional recurrence and disease-free
survival.[,] Three-dimensional conformal radiotherapy
(3D-CRT) is the most widely used method of treatment
planning and delivery at breast cancer RT. With
the improvements at RT planning systems and devices,
more conformal treatment plans have been achieved
and doses at organs at risk (OAR) have been avoided
using intensity-modulated radiotherapy (IMRT). Deep
inspiration breath hold (DIBH) technique is an essential
modern improvement for IMRT to achieve lower
mean heart doses and better protection of OAR.[,] In
the current practice, RT plannings of left-sided breast
cancer patients are performed with DIBH technique as
long as the RT devices are eligible to do so.
In the era of dosimetric optimization, homogenous
dose distribution and coverage at target volumes with
decreased high doses at OAR have been obtained with
these IMRT techniques.[-] Hence, similar local
control rates and survivals were reported with a lower
RT-related adverse effects.[-] Rotational IMRT
has been developed more recently. Volumetric-modulated
arc therapy (VMAT) or helical tomotherapy (HT)
is the forms of rotational IMRT at RT departments.
Better target volumes coverage and dose homogeneity
have been observed not in all patients, but also at patients
with complexity for RT planning.[-]
Although it is expected that new RT techniques
would allow the increase of the efficacy/toxicity ratio,
some unexpected dose distributions were encountered.
The low doses could occur in any region inside treatment
fields, even leading to higher OAR doses in some cases.
Patient anatomy is an important determinant, so it would
be the guide for the choice when comparing techniques.
This study aimed to present the results of comparison
of RT techniques at left-sided breast cancer patients.
Plans with field-in-field (FinF), dynamic-IMRT
(dIMRT), VMAT, and HT were compared for each patient
using the same planning contours to gather data
about target and OAR.
Methods
Data Selection
A single-institution, retrospective study was planned
to analyze the comparison of treatment plans. Ten patients
treated in the Department of Radiation Oncology between March 2023 and June 2023 were selected.
The inclusion criteria were the early stage left-sided
breast cancer, having breast-conserving surgery and no
chemotherapy treatment. Patients allowed to receive
hormonotherapy during RT. Median age of patients
is 54.10 years (range 42-73). Patients with breast implants
were excluded from the study.
Dosimetric Analysis
Patients were immobilized supine by C-Qual breast
board (Civco Medical Instruments Co. Inc. Coralville,
Iowa, USA) with the left arm above the patient's head.
Real-time Position Management (RPM, Varian Medical
Systems Inc., Palo Alto, USA) system was used for
the breath-holding method. An RPM localizer box was
placed on the skin between the chest and abdomen of
the patients and was followed by the cameras. All cases
were delineated by the same senior radiation oncologist
based on the images obtained for each patient with
a computed tomography (CT) simulator (Somatom
Force, Siemens Healthiners, Germany).
The clinical target volume was consisted of breast
tissue with the guidance of ESTRO and planning target
volume (PTV) was created by adding 5 mm margins in
all directions and cropped 3 mm under the skin. OAR
was defined as heart, left lung, contralateral breast, and
total lungs and delineated. Prescribed dose was 50 Gy in
25 fraction and optimization was based on the constraint
that ensuring 95% isodose line encompasses 95% of PTV.
Eclipse planning system (version 13.6, Varian Medical
Systems, Palo Alto, CA, USA) was used for FinF, dIMRT,
and VMAT plans. HT plans were calculated at HT planning
station (Radixact, Accuray Precision, version 3.3.1.2;
Sunnyvale, CA, USA). The different treatment techniques
have been applied to the patients" data set without any
clinical application. This activity does not require an ethical
approval according to our institution's rules.
The same criteria of biophysical dosimetric evaluation
for each structure were used. Dose-volume histograms
were calculated for each planning. The mean
doses, D2 and D98 doses of PTV, were recorded. Conformal
index (CI) and homogeneity index (HI) were
calculated. CI was defined as the quality of target dose
distribution, taking into account the dose inside versus
outside the PTV and HI was obtained from the
target D2, D50, and D98 doses.[,] The formulas
were chosen in such a way that the optimal value for
CI is 1 and for HI is 0. Mean doses of all OAR were
recorded and other factors as values for the percentage
of the left lung and total lungs that received 5 Gy
(V5) and 20 Gy (V20) were obtained.
Statistical Analysis
For descriptive statistics, mean±standard deviation was
used to present continuous data with normal distribution.
Median with minimum-maximum values was applied
for continuous variables without normal distribution.
Numbers and percentages were used for categorical
variables. The Paired Samples t-test was used for comparison
and analysis of the difference between any 2 of 4
plans. Data analysis and graphic presentations were performed
using the SPSS program, version 23.0 (SPSS Inc.).
Results
Average values of HI, CI, and mean doses OAR with
four different treatment plannings were summarized at
Tables 1 and 2. While Table 3 presents the comparison
between each plan and allows the significance, Table 4
shows the indices comparison of quality of plans with
HI and CI values.
Table 1 PTV coverage comparison
Table 2 OAR sparing and statistic values
Table 3 FinF vs dIMRT vs VMAT vs HT at OAR comparison
Table 4 FinF vs dIMRT vs VMAT vs HT for quality parameters
On two main quality indices, there was better homogeneity
for VMAT compared to FinF, but the comparison
of HI between others showed no significance.
All plannings were created with the aim for the good
homogeneity. Greater conformity for all intensitymodulated
techniques was reported compared to FinF.
Thus, CI 95% was improved in both dIMRT, VMAT,
and HT highly significantly, but non-significant difference
between dIMRT and HT was observed.
For the dose to the heart, lower mean doses were
achieved with the plans with FinF and HT techniques,
significantly. The highest mean heart doses were observed
with VMAT plans. HT plans showed the lowest
V20 both to the left lung and total lung. Furthermore,
FinF and dIMRT plans reported lower total lung V20
doses, but the left lung V20 doses were significantly
lowest with HT plans. The lowest V5 doses to the left
lung, total lung, and contralateral breast were observed
with FinF plans as expected. On the other hand, HT
plans showed no significant difference from FinF for
left lung V5 doses and significant lower left lung V5
doses from dIMRT and VMAT plans.
Discussion
The use of RT for breast cancer has become widespread
due to the high number of patients. For
achieving optimal results, modern RT techniques are
being used and have advantages from traditional RT
techniques. However, some caveats to these advances
were known and treatment planning has to be created
individually for each patient. The knowledge of
benefits of these modern RT techniques can help to
determine preferences at planning process.
The milestone of modern RT technique was IMRT
that has been used common at RT departments since
2000s. Afterward, arc treatments have been taken a
great part with the time and provided dose coverage
advantages at many cancer type. The results of this
trial indicated the comparison of these current modern
methods with FinF plannings, based on 3D-CRT
technique, and each other at left-sided breast cancer
simulated with DIBH technique.
In the left-sided breast irradiation, the aim is to
minimize the dose to the heart to decrease any late
cardiac toxicity.[] Many techniques have been tried
to achieve this low heart mean dose at RT departments,
and today each center has its own preferred
technique.[,,] Respiratory control is one the
most preferred and DIBH is easily adapted by patients.
Not only the advantage of eliminating movement
of respiratory for IMRT techniques, but also the
advantage of increasing distances between target and
OAR is concluded with DIBH. All the plans were created
on images obtained with DIBH technique during
CT simulation. Hence, both the anatomical regions
were ensured to be the same and the effect of the advantage
on each planning technique was observed.
Regarding dose conformity and homogeneity, there is
a clear theoretical advantage for IMRT, VMAT, and HT compared to 3D conformal techniques.[,,-]
CI and HI are considered important indicators for irradiation
plans quality and help to compare different
irradiation plans. However, the effect of these parameters
at clinically is inaccurately known. In the study,
VMAT has been reported as better for dose homogeneity
as expected, but the only significance was observed
between VMAT and FinF techniques. CI was superior
at HT treatments compared with 3DCRT and VMAT,
but similar with dIMRT. Hence, FinF technique as having
the least appropriately was concerned and HT was
the confluence of results.
Modern techniques usually consist great number of
beams to have better conformity and homogeneity often
at the expense of increased low-dose exposure for
the tissue surrounding the tumor. Increased percentage
of low dose bath may result in a higher risk of second
malignancies for long mean life expected patients.
[,] Comparison of techniques is having importance
in terms of both understanding the superior homogeneity
and conformity and minimized lower doses
at OAR and longer follow-ups will give us the result of
this low dose irradiation with advanced RT techniques.
In the analysis, lower doses at OAR had been observed
with FinF techniques as expected. However,
also HT plans provided low percentages, even more
than FinF plans at V20 values of lung. While HT was
reported as only significantly lower V20 for the left
lung, total lung V20 values were not significant between
HT, FinF, and dIMRT plans. In regard to V5
values, HT was seemed to lose advantage and FinF
plans were having lower V5 values for the left lung
and total lungs, but only significant for total lung
V5 value. The difference between FinF, dIMRT from
HT, and VMAT has been observed particularly at the
contralateral breast and contralateral lung, both receiving
relatively low dose.
In left-sided breast cancer irradiation, heart is
considered the most important OAR in terms of deterministic
late effects and risk of subsequent ischemic
events.[,,] Significant lower dose for
mean heart dose was observed with FinF and HT
techniques compared to dIMRT and VMAT. Whereas
the lowest mean heart dose would be expected with
the FinF technique, HT also had similar mean heart
doses. This may be a result of the new Radixact system,
because of new property of Radixact planning
system with definitive blockages descriptions. With
appropriate definitions and limitations of OAR, more
precise plans can be achieved at this rotational therapy
device. Likewise, significant lowest mean doses of
left lung V20, total lung V20, and left lung V5 were
reported with HT. The left lung also had the new described
advantage of this rotational treatment, but
naturally, this was concluded with further spread of
the low dose to surrounding organs. VMAT and HT
techniques both had significantly higher V5 doses at
contralateral breast and contralateral lung.
Conclusion
Comparison of four techniques at breast cancer radiotherapy
and the different advantages of treatment plans
were analyzed. As result, RT technique should be based
on the individual properties of the patient. Anatomic
complexities, age, disease factors, etc. are all that a radiation
oncologist takes into to give a decision.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Financial Support: None declared.
Authorship contributions: Concept - S.Y., D.P.; Design
- S.Y.; Supervision - E.D., F.A.; Funding - F.A.; Materials
- Z.G.; Data collection and/or processing - S.Y., D.P.; Data
analysis and/or interpretation - S.Y.; Literature search - S.Y.,
D.P.; Writing - S.Y.; Critical review - F.A.
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