Introduction
External beam radiotherapy (EBRT) plays an important
role in the treatment of gynecological cancers,
particularly in endometrial and cervical cancers. With the advances in RT technology, two-dimensional (2D)
EBRT has been replaced by three-dimensional conformal
RT (3DCRT), followed by intensity-modulated
RT (IMRT) and volumetric-modulated arc therapy
(VMAT). These conformal RT techniques have provided significant reductions in acute and late toxicity rates
without affecting the treatment outcomes in patients
with gynecological cancer.[] However, the planning
and delivery of RT are more complex for IMRT and
VMAT compared to conventional 3DCRT techniques
and are susceptible to errors. Therefore, it is recommended
to perform patient-specific IMRT and VMAT
quality assurance (QA) techniques to detect errors.[]
Patient-specific QA in IMRT is often performed before
treatment. In particular, errors due to variability in
the patient's anatomy, tumor morphology, and the position
of the organs at risk (OARs) relative to the target
volume cannot be detected by pre-treatment QA.[]
Therefore, the quality of actual treatment remains
unclear. In vivo dosimetry is a solution for ensuring
the accuracy of the RT delivery. This accuracy can be
tested with optically stimulated luminescence dosimetry
(OSL), thermoluminescence dosimetry (TLD),
film dosimetry, and electronic portal imaging device
(EPID).[-] While OSL and TLD measure the point
dose, film dosimetry has the capability to measure the
2D dose distribution. The EPID on the other hand is
a digital MV imaging detector originally designed for
the verification of patient positioning during treatment.
Due to its dosimetric properties, it can also be utilized
in patient-specific QA measurements. Recently, EPIDbased
systems are used as in vivo dosimetry systems,
since they include the transit dose information.[-] In
recent years, EPID-based 3D in vivo dosimetry is increasingly
used in routine practice. However, data on
gynecological patients are still very limited. Since the
OARs as the bowel, urinary bladder, and rectum can
move and change in shape and dimensions during treatment,
the proximity of these OARs to the target volume
increases the importance of in vivo dosimetry for gynecological
cancers. The variations during treatment can
affect the doses to the target and OARs which can result
in increased toxicity and decreased local control rates.
In this study, 3D in vivo EPID-based in vivo dosimetry
results were examined in patients with endometrial
and cervical cancer previously treated in our clinic
and a phantom study was additionally performed. The
performance and reliability of EPID-based system were
evaluated in 3D in vivo QA of gynecological patients.
Methods
In this study, we performed a retrospective analysis of
dose distribution in our patients who were treated with
external pelvic RT for endometrial (n=10) or cervical (n=10) cancer. This study was approved by Institutional
Review Board (Project no: GO 22/294). The RT planning
and 3D in vivo dosimetry data were abstracted
from the treatment planning system (TPS) and iView-
Dose® (Elekta, Crawley, UK) in vivo QA system.
In Vivo Measurements
Daily kV cone-beam CT (CBCT) was acquired for
each patient. After the positional accuracy was approved,
the treatment was started. During treatment,
the EPID was in the open position and the transit radiation
was collected using the iViewGT® (Elekta, Crawley,
UK) software. We used an EPID with amorphous
silicon flat panel-type imager (Elekta iViewGT®). The
sensitive area of the panel contains 1.024×1.024 pixels
which can image up to a 26×26 cm2 field size at the
isocenter. The collected data were automatically transferred
to the iViewDose® (Elekta, Crawley, UK) in vivo
QA system. The iViewDose® software can reconstruct
the transit dose to the CT images of the patient. In a
previous paper, the mathematical aspects of the dose
reconstruction algorithm were explained.[] The
iViewDose® also allows performing 3D gamma analysis
between the TPS and measured dose. The gamma
index (γ) is one of the most commonly used metrics
for analyzing the fidelity of IMRT and VMAT plans.
It quantifies the difference between measured and calculated
dose distributions on a point-by-point basis in
terms of both distance to agreement (DTA) and dose
differences. The mathematical structure of gamma
analysis was previously introduced by Low et al.,[] in
which γ was defined as in Eq.(1).
γ(rm)=min{⌈(rm,rc)}∀{rc}, (1)
Where the pass-fail criteria are
γ(rm)≤1, calculation passes,
γ(rm)>1, calculation fails. (2)
In this study, we used 3D gamma evaluation per
fraction for analysis. The mean value of the gamma
distribution (γmean), the 1% of points have an equal or
higher gamma value (γ1%) and the criteria of 3% dose
difference/3mm DTA (γ≤1%) were examined to evaluate
the treatment quality. The pass rate criterion was
described as 0.7, 2.0, and 90%, respectively.
The dose reference point (DRP) values were used
for the comparison of point dose measurement results.
The software allows us to select a structure to define the
DRP which is placed in the mass center of the delineated
structure. For the selected structures, the algorithm of the
iViewDose® software calculates the percentage dose difference
between the TPS and EPID doses reconstructed
on the treatment CT. The acceptance criterion was set at
within 3% dose difference for the planning target volume.
Phantom Measurements
Patient-specific phantom measurements were carried
out with the Alderson Rando phantom. The phantom
measurement was performed to confirm that the
treatment plans were deliverable. For this purpose, the
plans were exported to the Alderson Rando phantom"s
CT. VMAT plans were re-calculated and irradiated on
that phantom to perform gamma analysis verification
with the passing criterion of 3% (global)/3 mm. Following,
the measurement was compared with the TPS
using the iViewDose® software.
Results
Phantom Measurements
The gamma analysis results of the phantom measurements
are given in Table 1. There was a good agreement
between the EPID doses and TPS. While the mean
gamma passing rate was 97.2±2 for the endometrial
cancer plans, it was observed as 98.3±1.8 for the cervical
cancer plans. The results showed that all treatment
plans were applicable.
Table 1: Dosimetric differences for phantom data (90%
passing rate was considered clinically acceptable)
In Vivo Measurements
The results for in vivo measurements are given in Table
2. All patients met the passing criteria for γmean, γ1%, γγ1%,
and DRP. The mean gamma passing rate was 95.1%±1.7 and 96.3%±2.9 for patients with the endometrial and
cervical cancer, respectively. While the mean dose difference
at the isocenter in percentage was 1.42±0.94
for patients with endometrial cancer, it was observed
1.59±0.78 for patients with cervical cancer. The maximum
dose difference for the DRP was 2.58% for endometrial
and 2.55% for cervical cancer, respectively.
Table 2: Dosimetric differences for patient data
Figure 1 displays an example of the TPS dose, EPID
dose, gamma analysis results, and dose distributions
along the central axis. The blue color in gamma analysis
indicates that the difference between the calculated
(TPS dose) and measured dose (EPID) is very small.
On the contrary, the red color indicates that the region
where the difference between the calculated and measured
dose exceeds the acceptance criteria. The dose
distribution along the central axis also shows that the
difference between the calculated and measured dose is
very small in and out of the field.
Fig 1: Calculated dose, measured dose, gamma evaluation, and line dose comparison of calculated and measured dose on
the central axis for an endometrial and a cervical cancer patient.
TPS: TPS: Treatment planning system; EPID: Electronic portal imaging device; DRP: Dose reference point.
Discussion
This article aims to show the performance of the EPID
for in vivo dosimetry of patients with gynecological
cancer. Previously, the performance of in vivo EPID
dosimetry for various cancer types was investigated.
[-] However, the data on patients with gynecological
cancer are still scarce. We clinically implemented
the 3D in vivo EPID-based dosimetry QA for patients
treated with VMAT. In our study, the gamma analysis
passing rates were in tolerance levels for all patients.
We think that the most important reasons for obtaining
good results are the patient position verification through CBCT and our strict bowel and rectal protocol
for every patient and every fraction which allow minimizing
the dosimetric differences due to anatomical
and positional changes.
The mean gamma analysis passing rate for phantom
measurements was 97.2% and 98.3% for the patients
with endometrial and cervical cancer, respectively. On
the other hand, in vivo patient calculation results were
95.1% and 96.3% for endometrial and cervical cancer,
respectively. The decrease in the passing rate may be
due to the heterogeneity of the pelvic region which may
have caused computational errors in the TPS. Since
the pelvic region of the phantom consists only of bone
and soft-tissue-equivalent materials, errors due to the
calculation algorithm may therefore be fewer in the
phantom. Another reason for observing this result may
be the intrafractional variation due to organ deformation
and/or movement. The intrafraction variations are
smaller compared with the interfraction variations but
are still of relevance in clinical practice. Although, patients
are given detailed instructions to empty the rectum
and fill the bladder and checked through CBCT, vaginal motion, and bladder and rectal volume changes
can occur during treatment. To minimize the target
motion, the use of intracavitary applicators was suggested
for IMRT treatment of gynecological malignancies
in clinical practice.[,] Cilla et al.[] reported
the agreement between the calculated and measured
doses for this practice, where they performed the study
with an ion chamber. As a future work, testing the accuracy
of this practice can be performed with EPID in 3D.
In this study, we did not encounter any machinerelated
or patient-related errors that may have adversely
affected the results. The previous studies
showed that in vivo EPID measurements have the
potential to detect treatment delivery errors.[-]
Mans et al.[] reported 3D in vivo verification of
4337 patients that consisted of 1319 breast, 1018 prostate,
602 rectum, 543 head and neck, 454 lung, and
401 other cancer cases. Seventeen serious errors were
detected among the treatment plans which were classified
as patient anatomy (n=7), plan transfer (n=4),
suboptimally tuned TPS parameter (n=2), accidental
plan modification (n=2), failed delivery (n=1), and dosimetrically undeliverable plan (n=1). Other studies
were also conducted to search the possible errors
that could be detected by in vivo EPID measurements.
[,] Previously, we[] investigated the error detection
capability of in vivo EPID measurements for
the stereotactic body RT applications for prostate
cancer. Our results showed that the EPID can detect
the errors based on linear accelerator calibration,
MLC positions, and patient anatomy.
One of the limitations of in vivo EPID-based dosimetry
is the radiation field size. Since the maximum
effective field size of the EPID at the isocenter
is 26×26 cm2, the QA of the radiation fields above this
size is not possible. In particular, in a patient with gynecological
cancer that has para-aortic lymph node
involvement and needs to be irradiated with extended
field irradiation exceeds, this limitation for whom
EPID-based dosimetry is not suitable. However, Kim
et al.[] designed a study using Halcyon® 2.0 (Varian
Medical Systems, Palo Alto, CA, USA) machine
to treat the extended fields using IMRT with dualisocenter
in patients with gynecological cancer since
Halcyon® 2.0 is capable of treating >28 cm treatment
length using a dual isocenter. Their results showed
that Halcyon® EPID-based in vivo dosimetry has the
potential to function for complex IMRT and adaptive
RT. They detected interfraction variations in random
patterns depending on internal organ motion and
source to skin distance change.
The advantage of EPID-based dosimetry over other
systems is that it does not need extra time for application
since the QA measurements are performed during
treatment. In addition, QA can be easily applied in
each fraction. If we assume that a pre-treatment QA
for a patient takes 10 min, we saved approximately 200
min for 20 patients in the present study. It does not
only save the physicist's time but also reduces on-time
of the treatment machine.
Previously, few studies reported in vivo measurement
results by the placement of dosimeters into
the body cavities for pelvic RT which has the disadvantage
of patient discomfort. The TLD and diodes
were the most commonly used dosimeters in these
studies. However, diode detectors are not suitable
for IMRT or VMAT as the diode detector response
exhibits orientation dependence. Diode sensitivity is
reported to vary by up to 15% depending on gantry
orientation.[] Weber et al.[] reported the results
of patients with anal cancer undergoing in vivo
dosimetry by TLD inserted at the center of the anal
verge. The measured doses differed by an average of
6% compared to the TPS along the central axis. In
general, the acceptance criterion is within ±10% for
the TLD.[] For the EPID-based system, this acceptance
range is narrow. In the present study, the
acceptance criterion of ±3% was used for point dose
measurements with the EPID and all measurements
were consistent with this criterion.
Conclusion
The EPID-based in vivo dosimetry can be used in the
clinical routine for gynecological cancers. The workload
with this approach is minimal and it saves time.
The agreement between the measured and computed
doses indicates that VMAT delivery for gynecological
cancers is safe in case the patient setup variations are
minimized. In vivo point measurements showed that
the measured and calculated doses were in agreement
with ±3% dose differences for pelvic irradiation. The
main limitation of in vivo EPID-based dosimetry is the
radiation field size for gynecological cancers.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: The study was approved by
the Hacettepe University Non-Invasive Clinical Research
Ethics Committee (no: 2022/05-36, date: 15/03/2022).
Financial Support: None declared.
Authorship contributions: Concept - Y.Y.; Design - Y.Y.;
Supervision - Y.Y., S.Y.S.; Funding - None; Materials - S.Y.S.,
M.G., F.Y.; Data collection and/or processing - Y.Y., S.Y.S.,
M.G., F.Y.; Data analysis and/or interpretation - Y.Y., S.Y.S.,
M.G., F.Y.; Literature search - Y.Y., S.Y.S., M.G., F.Y.; Writing -
Y.Y., S.Y.S., M.G., F.Y.; Critical review - Y.Y., S.Y.S., M.G., F.Y.
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