METHODS
Treatment plans for retinoblastoma patients were created utilizing IMRT, VMAT-F, and VMAT-P techniques.
The prescription dose was set at 45 Gy in 25 fractions. An analysis was conducted on dosimetric
parameters using the cumulative dose-volume histogram (cDVH), including Planning Target Volume
(PTV) coverage (D95%), Conformity Index (CI), Homogeneity Index (HI), and the radiation doses
received by organs at risk (OARs). Additionally, brain dose-volume metrics (V5Gy, V10Gy, V15Gy) and
monitor units (MUs) were evaluated and compared among the three methods.
RESULTS
All treatment techniques achieved 95% coverage of the prescribed dose within the PTV volume. The
VMAT methods significantly improved both the mean and maximum PTV doses compared to IMRT
(p<0.001). Among the VMAT techniques, VMAT-P achieved the highest Conformity Index (1.00±0.01)
and the lowest Homogeneity Index. Additionally, VMAT-P markedly decreased the volume of brain receiving
10 Gy (12.9±2.96%) and 15 Gy (6.78±1.82%) compared to both IMRT and VMAT-F (p<0.001).
IMRT was more effective in preserving contralateral structures, particularly the eyes and lenses. Furthermore,
both VMAT techniques utilized fewer monitor units than IMRT (p<0.001).
CONCLUSION
In this study, VMAT-P achieved an advantageous balance among PTV coverage, conformity, and the
preservation of organs at risk (OARs). It exhibited better conformity and improved sparing of brain
tissue at moderate dose levels compared to both IMRT and VMAT-F.
Keywords: Intensity Modulated Radiotherapy; retinoblastoma cancer; volumetric modulated arc therapy
The main objective in managing retinoblastoma
(Rb) is to ensure survival. Treatment options have significantly
advanced and now encompass external beam
radiotherapy (EBRT), plaque radiotherapy, multiple
chemotherapy approaches (including intravenous, intra-
arterial, intravitreal, and intracameral), as well as
consolidation therapies like cryotherapy and transpupillary
thermotherapy.[
Currently, radiation therapy is mainly employed after
other treatment options have been exhausted or when
tumors are too large for localized surgical intervention.
With its lower recurrence rates, EBRT has emerged as a
prevalent treatment choice for extraocular cancer, particularly
in comparison to radioactive plaque brachytherapy.[
Historically, three-dimensional radiotherapy employed
anterior and lateral wedge-shaped fields for
treatment; however, this approach resulted in dose inhomogeneity
within the target area. Recent advancements
in irradiation techniques, such as Intensity Modulated
Radiotherapy, Volumetric Modulated Arc Therapy, and
Proton Radiotherapy, facilitate a more conformal dose
distribution to the target volume while minimizing exposure
to adjacent healthy tissues.[
Previous research has explored the capabilities and
advantages of Volumetric Modulated Arc Therapy
(VMAT) in the management of intraocular cancer, yielding
encouraging outcomes.[
Computed tomography (CT) images were obtained with a slice interval of 1.2 mm using the GE Revolution EVO from GE Healthcare Pvt. Ltd. The DICOM images from these CT scans were utilized to delineate the clinical target volume (CTV), which encompassed the orbit, optic canal, superior orbital fissure, and inferior orbital fissure. The planning target volume (PTV) was established as the CTV plus a uniform three-dimensional margin of 3 mm. The organs at risk included the contralateral eye, lens, optic nerve, optic chiasm, pituitary gland, bilateral cochlea, and brainstem.
The Eclipse Treatment Planning System Version 16.0.14, developed by Varian Medical Systems, Inc. in Palo Alto, CA, USA, was employed to formulate three distinct treatment plans for each patient. These plans were retrospectively designed using a Varian True- Beam SVC linear accelerator, which is outfitted with a Millennium 120 multi-leaf collimator (MLC).
The study examined three different planning methods. The initial plan featured a 5-field Intensity-Modulated Radiation Therapy (IMRT) setup, incorporating specific gantry angles of 0°, 320°, 240°, 195°, and 20°. The second plan, designated as Full Arc Volumetric Modulated Arc Therapy (F-VMAT), involved a single clockwise VMAT arc ranging from 181° to 179°, with a collimator angle set at 30°. The third plan implemented the dual-partial arc Volumetric Modulated Arc Therapy (PVMAT) technique, where the gantry rotation was modified in both clockwise and counterclockwise directions to suit the dimensions and concavity of the Planning Target Volume (PTV). Additionally, the collimator angles were adjusted to ±30° to enhance treatment efficacy.
A 6 MV photon beam was utilized across all plans. The prescribed treatment dose was 45 Gy, delivered in 25 fractions of 1.8 Gy each over a span of 5 weeks. The Anisotropic Analytic Algorithm (AAA, version 16.0.14) with a grid spacing of 2.5 mm was employed for the final dose calculations. The objective of the planning was to ensure that 95% of the prescribed dose (PD) reached 95% of the PTV, while limiting the volume of the PTV receiving 107% of the PD to no more than 1%.
For the organs at risk (OARs), the maximum dose constraints were established as follows: brainstem, optic chiasm, and contralateral optic nerves receiving less than 54 Gy; contralateral lens with a maximum dose (Dmax) of less than 2 Gy and a mean dose (Dmean) of less than 6 Gy; and contralateral eye with a Dmax of less than 45 Gy and a Dmean of less than 20 Gy.
The quality indices of the plans were evaluated by analyzing the dose-volume parameters obtained from the cumulative dose-volume histograms (DVH) generated for each specific plan.
Conformity Index
CI=VRI/TV
Homogeneity Index
HI=(D2%-D98%)/D50%
HI=0 implies a completely homogeneous dose distribution.
Conformation Number
CN=(TVRI × TVRI)/(TV × VRI)
In this equation, TVRI represents the target volume
covered by the reference dose in cubic centimeters
(cc), TV represents the total target volume in cc, and
VRI represents the volume of the reference dose in cc.
CN=1 if the plan is perfect.
Additionally, MUs for each treatment plan were
also recorded for comparison.
Statistical Analysis
The conformity index (CI) is defined as the prescribed
isodose volume (VRI) divided by the total PTV volume.
The recommended value is one but is usually <1.
It is defined as follows:[
The homogeneity index (HI) was calculated as the difference
between the delivered dose for 2% (D2%) and
98% (D98%) of the PTV volume, divided by the dose
for 50% of the PTV volume (D50%). It is defined as
follows:[20]
PD coverage in treatment plans can be assessed using
a ratio.[20] This ratio, known as the Conformation
Number (CN), is defined as follows:
The statistical findings are presented as mean±standard
deviation (SD). Statistical calculations were conducted
using Microsoft Excel. A two-tailed paired Student's
t-test was utilized to assess the significance of the observed
differences. Differences between the two methods
are deemed statistically significant when the probability
value (p) is less than or equal to 0.05.
IMRT: Intensity-modulated radiation therapy; VMAT-P: Partial-arc volumetric modulated arc therapy; VMAT-F: Full-arc volumetric
modulated arc therapy.
IMRT: Intensity-modulated radiation therapy; VMAT-P: Partial-arc volumetric modulated arc therapy; VMAT-F: Full-arc volumetric
modulated arc therapy.
PTV and Dosimetric Parameters
The implementation of IMRT led to a markedly lower
maximum dose (Dmax) to the planning target volume
(PTV) compared to both VMAT-P (p=0.001) and
VMAT-F (p<0.001). The PTV demonstrated clinically
acceptable coverage across all three treatment modalities,
with D95% values recorded as 95.84±1.29
for IMRT, 97.37±0.42 for VMAT-P, and 96.86±1.05
for VMAT-F. Statistically significant differences were
noted with p=0.001 for IMRT versus VMAT-P and
p<0.001 for IMRT versus VMAT-F. However, the comparison
between VMAT-P and VMAT-F did not yield
a statistically significant result (p=0.059).
Furthermore, the average dose (Dmean) administered to the PTV was significantly lower in IMRT (44.39±0.31) compared to both VMAT techniques, which recorded Dmean values of 44.99±0.05 for VMAT-P and 44.99±0.48 for VMAT-F, with p<0.001 for both comparisons. No significant difference in Dmean was found between VMAT-P and VMAT-F (p=0.944). Additionally, there were no notable differences in the volume receiving 107% of the prescribed dose (V107%) across the three techniques, as all comparisons yielded p-values exceeding 0.05 (p=0.059).
The Conformity Index (CI) demonstrated a notable enhancement (approaching 1) with VMAT-P (1.00±0.01) when compared to IMRT (1.03±0.05, p=0.043) and VMAT-F (1.01±0.01, p=0.007). No significant difference was found between IMRT and VMAT-F (p=0.156). The Homogeneity Index (HI) revealed no significant difference between IMRT and VMAT-P (p=0.696); however, VMAT-F (0.09±0.03) showed a significantly greater HI than VMAT-P (0.07±0.01, p=0.01). The difference between IMRT and VMAT-F was not statistically significant (p=0.072).
The Conformation Number (CN) was significantly higher for both VMAT techniques compared to IMRT (IMRT: 0.81±0.05, VMAT-P: 0.88±0.04, VMAT-F: 0.89±0.05; p=0.001 for IMRT vs. VMAT-P, p=0.004 for IMRT vs. VMAT-F). No significant difference was observed between VMAT-P and VMAT-F (p=0.204).
The monitor units (MUs) utilized in the techniques of IMRT, VMAT-P, and VMAT-F were analyzed. The average MU values recorded were 565.09±54.17 for IMRT, 440.31±44.07 for VMAT-P, and 468.48±72.73 for VMAT-F. Statistical analysis indicated that VMAT-P required a significantly lower number of MUs compared to IMRT (p<0.001). Conversely, there was no significant difference in the number of MUs between VMAT-P and VMAT-F (p=0.244). Additionally, IMRT demonstrated a significantly higher number of MUs when compared to VMAT-F (p<0.001).
Organ at Risk (OAR)
Table
Brainstem and Optic Chiasm
For the brainstem, the maximum dose (Dmax) values
recorded were 36.51±12.88 Gy for Intensity-Modulated
Radiation Therapy (IMRT), 35.49±10.33 Gy for
Volumetric Modulated Arc Therapy with a partial arc
(VMAT-P), and 35.66±9.64 Gy for Volumetric Modulated
Arc Therapy with a full arc (VMAT-F). Similarly,
the Dmax values for the optic chiasm were found to be
41.6±6.63 Gy for IMRT, 40.90±8.70 Gy for VMAT-P,
and 41.3±7.78 Gy for VMAT-F. No significant statistical
differences were observed, as all methods for both
structures yielded p-values greater than 0.05.
Contralateral (C/L) Optic Nerve
The maximum dose (Dmax) values recorded for the contralateral
optic nerve were 9.44±4.54 Gy for IMRT, 17.52±3.91
Gy for VMAT-P, and 29.74±42.25 Gy for VMAT-F. A statistically
significant difference was noted between IMRT and
VMAT-P (p<0.001). In contrast, no significant differences
were found between VMAT-P and VMAT-F (p=0.336) or
between IMRT and VMAT-F (p=0.124).
C/L Eye and Lens
Regarding the maximum dose administered to the contralateral
eye, the intensity-modulated radiation therapy
(IMRT) delivered an average of 6.32±2.20 Gy, while
the volumetric modulated arc therapy with partial arcs
(VMAT-P) provided 5.05±1.92 Gy, and the full arcs
variant (VMAT-F) delivered 6.14±2.26 Gy. Statistical
analysis revealed no significant differences between IMRT and VMAT-P (p=0.175) or between IMRT and
VMAT-F (p=0.810). However, a significant difference
was noted between VMAT-P and VMAT-F (p=0.037),
with VMAT-P resulting in a lower dose. For the contralateral
eye, the average radiation doses recorded were
1.57±0.34 Gy for IMRT, 2.26±0.63 Gy for VMAT-P, and
2.36±0.67 Gy for VMAT-F. Both VMAT-P and VMAT-F
delivered significantly higher doses compared to IMRT,
with p-values below 0.001 for each comparison. No significant
difference was found between VMAT-P and
VMAT-F, as indicated by a p-value of 0.067.
The maximum dose delivered to the contralateral lens was measured at 1.81±0.39 Gy for IMRT, 2.03±0.39 Gy for VMAT-P, and 2.20±0.40 Gy for VMAT-F. The dose associated with VMAT-P was significantly higher than that of IMRT (p=0.009), and VMAT-F also demonstrated a significant increase compared to IMRT (p=0.001). However, no significant difference was found between VMAT-P and VMAT-F (p=0.063). Regarding the mean dose, the values recorded for the contralateral lens were 1.30±0.29 Gy for IMRT, 1.71±0.30 Gy for VMAT-P, and 1.75±0.31 Gy for VMAT-F. Both VMAT-P and VMAT-F showed significantly elevated doses in comparison to IMRT (p<0.001 for both). There was no significant difference noted between VMAT-P and VMAT-F (p=0.497).
Brain Dose-Volume Parameters
This study analyzed the brain dose volumes associated
with IMRT, VMAT-P, and VMAT-F techniques. The
results for V5Gy indicated that the percentage of brain
volume receiving at least 5 Gy was 24.7±4.51% for IMRT,
26.2±4.91% for VMAT-P, and 27.8±5.28% for VMAT-F.
Statistically significant differences in V5Gy were observed
between IMRT and VMAT-F (p<0.001) as well
as between VMAT-P and VMAT-F (p=0.005), while
no significant difference was found between IMRT and
VMAT-P (p=0.059). Regarding V10Gy, the brain volume
percentages receiving a minimum of 10 Gy were
14.5±2.70% for IMRT, 12.9±2.96% for VMAT-P, and
16.6±3.65% for VMAT-F. VMAT-P demonstrated a statistically
significant reduction in V10Gy compared to
IMRT (p<0.001), whereas VMAT-F exhibited a significant
increase in V10Gy relative to VMAT-P (p<0.001).
Furthermore, V10Gy was significantly greater with
VMAT-F than with IMRT (p=0.003). For the V15Gy
parameter, the percentages of brain volume receiving at
least 15 Gy were 8.38±2.10% for IMRT, 6.78±1.82% for
VMAT-P, and 8.54±17.26% for VMAT-F. VMAT-P revealed
a statistically significant decrease in V15Gy compared
to IMRT (p<0.001). Conversely, no significant
differences were noted between VMAT-P and VMAT-F
(p=0.002), or between IMRT and VMAT-F (p=0.77).
The assessment of IMRT, VMAT-P, and VMAT-F concerning the planning target volume (PTV) revealed several notable distinctions. VMAT-P demonstrated a significantly higher Dmax in comparison to IMRT (p=0.001), while the difference between VMAT-P and VMAT-F was not statistically significant (p=0.059). Conversely, VMATF exhibited a Dmax that was significantly greater than that of IMRT (p<0.001). Regarding Dmean, both VMAT-P and VMAT-F presented similar mean doses, which were significantly elevated compared to IMRT (p<0.001). No significant differences were observed in V107% among the techniques (p>0.05). VMAT-P achieved a significantly higher D95% than IMRT (p=0.001), and VMAT-F also exceeded IMRT in D95% (p<0.001).
Moreover, VMAT-P had a superior Conformity
Index relative to both IMRT (p=0.043) and VMATF
(p=0.007), with no significant difference between
VMAT-P and VMAT-F (p=0.156). Additionally,
VMAT-P surpassed VMAT-F in terms of the Homogeneity
Index (p=0.01). Figure
IMRT: Intensity-modulated radiation therapy; VMAT-P:
Partial-arc volumetric modulated arc therapy; VMAT-F:
Full-arc volumetric modulated arc therapy.
The results of this study indicate that the VMAT-P
technique achieves a modest decrease in radiation exposure
to the brainstem and optic chiasm when compared
with IMRT and VMAT-F. Specifically, VMAT-P demonstrates
a 2.79% reduction in dose for the brainstem and
a 1.68% reduction for the optic chiasm in comparison
to IMRT, along with reductions of 0.48% and 0.97%, respectively,
when compared to VMAT-F. These findings
align with previous studies, including those conducted by
Zhang et al.[
The findings of the study demonstrate a notable increase
in the radiation dose delivered to the contralateral
(C/L) optic nerve when employing VMAT-P, which
is measured at 85.60% in contrast to IMRT. Furthermore,
an additional elevation is noted with VMAT-F,
recorded at 69.35% in relation to VMAT-P during the
treatment of retinoblastoma. This situation raises significant
concerns, as elevated radiation exposure to the
optic nerve may result in vision impairment and other
complications. Previous studies have corroborated these
findings, with one investigation indicating that VMAT
yields higher doses to the optic nerve compared to
IMRT, especially when utilizing full arc VMAT. Moreover,
another study has shown that partial arc VMAT successfully minimizes the radiation dose to both the
optic nerve and retina when compared to full arc VMAT.
The findings of our study are consistent with previous
studies that demonstrate VMAT results in higher radiation
doses to the contralateral lens compared to IMRT.
For example, Zhang et al.[
This study examined cochlear sparing in the treatment
of retinoblastoma utilizing IMRT, VMAT-P, and
VMAT-F techniques. The results indicated that VMATP
significantly decreased the maximum dose delivered
to the left cochlea in comparison to IMRT (p=0.044).
Nevertheless, no significant differences were observed
between VMAT-P and VMAT-F, nor between IMRT
and VMAT-F. These results align with studies conducted
by Wang et al.[
Our study indicates that VMAT-F results in a greater
brain volume exposed to doses of ≥5 Gy, as shown in Figure
4a, whereas VMAT-P is associated with a decrease in
brain volume receiving ≥10 Gy and 15 Gy, as shown in
Figures
The results of our study indicate that VMAT-P necessitates
a considerably reduced number of monitor units
(MUs) compared to IMRT in the treatment of retinoblastoma,
with VMAT-P utilizing 30% fewer MUs compared
to IMRT (p<0.001), as illustrated in Figure
The findings presented hold significant implications
for clinical practice. The enhanced dose conformity and
reduced exposure to vital anatomical structures achieved
through VMAT, particularly VMAT-P, may lead to better
tumor control and a lower likelihood of long-term adverse effects. This is especially crucial for pediatric
patients diagnosed with retinoblastoma, where minimizing
late toxicities is of utmost importance. Additionally,
the possibility of shorter treatment durations with
VMAT could improve patient adherence and lessen the
necessity for anesthesia in younger individuals. Future
research should focus on validating the dosimetric advantages
in larger cohorts and assessing their influence
on clinical outcomes. Long-term comparative studies between
VMAT and IMRT, concentrating on factors such
as tumor control, preservation of vision, and incidence
of secondary cancers, would yield valuable insights. Furthermore,
exploring the potential integration of VMAT
with other advanced treatment modalities, such as proton
therapy or stereotactic radiotherapy, could further
refine treatment approaches for retinoblastoma.
IMRT: Intensity-modulated radiation therapy; VMATP:
Partial-arc volumetric modulated arc therapy;
VMAT-F: Full-arc volumetric modulated arc therapy.
IMRT: Intensity-modulated radiation therapy; VMAT-P:
Partial-arc volumetric modulated arc therapy; VMAT-F:
Full-arc volumetric modulated arc therapy.
Authorship contributions: Concept - D.P., M.K.Z., R.M.; Design - D.P., M.K.Z.; Supervision - M.K.Z.; Data collection and/or processing - D.P., M.K.Z., R.M.; Data analysis and/or interpretation - D.P., M.K.Z.; Literature search - M.K.Z., D.P., R.M.; Writing - M.K.Z., D.P.; Critical review - M.K.Z., R.M., D.P.
Conflict of Interest: All authors declared no conflict of interest.
Use of AI for Writing Assistance: No AI technologies utilized.
Financial Support: None declared.
Peer-review: Externally peer-reviewed.
