] There is a long survival expectancy in similar
patients and long-term side effects such as secondary
malignancy are important in these patient groups.
Which technique is better for low-dose areas, often neglected
in current guidelines, is a topic of current debate.
In this study, different techniques were compared
in terms of low dose distribution.
In this case report, the HyperArc planning technique,
which is a technique generally preferred in stereotactic
RT, was tried to be applied in benign disease,
in a large RT area, and with a low dose. In this study, it
was aimed to dosimetrically compare the HA treatment
planning algorithm with 3D Conformal Radiotherapy
(3DCRT), VMAT, and Helical IMRT techniques in the
RT of a patient diagnosed with Graves" Ophthalmopathy.
In addition, the patient's short-term treatment results
are presented.
A 39-year-old female patient, who was followed up
for 1 year due to hyperthyroidism and was using Methimazole
(10 mg/day), was admitted to the hospital
with eye pain in November 2020. The patient, who was evaluated in detail by the ophthalmology and endocrine
department, was diagnosed with TO, and steroid
therapy (prednol 72 mg/day) was started for treatment.
In the 2nd month follow-up after steroid treatment, it
was observed that eye pain continued and limitation of
eye movements developed. In addition, diabetes mellitus
and Cushing's disease were observed due to highdose
steroids. The dose was reduced in steroid therapy
for side-effect control. The patient was evaluated in the
multidisciplinary council, and it was decided to continue
the treatment with RT. In orbital MRI before RT, an
appearance compatible with proptosis and an increase
in the bilateral retro-orbital adipose tissue thickness
were observed after the contrast agent injection with
edema in T2 sequences reaching 10 mm in the thickest
part of the extraocular muscles (Fig. 1). Simulation
computed tomography (CT) was performed on the patient
with a slice thickness of 1.25 mm. Extraocular eye
muscles and retrobulbar adipose tissue are contoured
as the Clinical Target Volume. The lens, optic chiasma,
lacrimal gland, macula, brain, pituitary gland, and hippocampus
were contoured as organs at risk. Due to the
patient's young age and long life expectancy, RT plans
were tried with different devices and algorithms to reduce
the risk of treatment-related complications.
Fig 1: Patient's pre-radiotherapy orbital MRI.
MRI: Magnetic resonance imaging; RHP: Right head-posterior;
LFA: Left foot-anterior.
The 3DCRT, VMAT, and HA plans were created
by using the VARIAN planning system; the helical
IMRT plan was obtained using the RadixAct. In treatment plans, it is aimed that 95% of the target volume
receives 95% of the prescribed dose. The degree of
importance of the organ at risk was reported to the
medical physicist who planned the RT (1. Lens, 2.
Frontal Lobe, 3. Macula, 4. Lacrimal gland) and critical
organ dose comparisons were given in Table 1 and
Fig. 2. The plans were compared in detail, then the patient
was treated with the HA plan as it provided the
most negligible OAR doses and optimal target organ
dose-volume values. The target volume dose coverage was better and the frontal lobe, macula, lens dose,
and gradient index were lower in the plan performed
with the HA technique compared to 3DCRT, helical
IMRT, and VMAT. Although the lens dose was found
to be lower in the Helical IMRT plan, because the
dose coverage was low and the calculated treatment
time was long, HA treatment was found to be more
appropriate. During the 2-week treatment period, RT
was administered with a fractional dose of 2 Gy and
a total dose of 20 Gy. Pain situations were questioned
at the beginning of RT, on the 6th day (mid-treatmentwhen
a total of 10 Gy has been completed), and at
the end of RT. The eye was examined to evaluate the
limitation of movement. Methylprednisolone (8 mg/
day) was given to the patient during the treatment.
Although the patient describes a significant reduction
in pain during the treatment process, there is minimal
improvement in eye movement limitation. At
the end of the treatment, an ocular CT scan showed
a decrease in edema of the extraocular muscles (Planning
CT: EOM R:7.1 cc EOM L:7.7 cc, 2nd month CT:
EOM R:6.5 cc EOM L:7.1cc). In the 2nd month followup of the patient after RT, a decrease in eye pain and
preorbital edema and a significant improvement in
eye movement limitation were observed compared to
pre-RT. The patient was questioned in terms of side
effects, and no acute side effects were observed. Close
follow-up of the patient by ophthalmology and endocrine
clinics continues.
Table 1: Dose distributions obtained in plans made with different planning techniques
Fig 2: Dose distribution of the patient in different planning techniques with 50% isodose line in green.
A: 3DCRT; B: VMAT; C: TOMOTHERAPY; D: HA. 3DCRT: 3D Conformal Radiotherapy; VMAT: Volumetric Arc Therapy; HA: Hyperarc.
Orbital RT has been used in the treatment of TO
since 1915.[,] In the past, irradiations were applied
with the Lateral Counter-Field (LOF) technique
due to its easy setup and fast application procedures. In
this technique, since a block was placed in the anterior
part to protect the lens, the entire target volume did
not receive an effective dose, and a homogeneous dose
distribution could not be achieved. In the first studies,
conventional RT was used by opening two lateral areas
from the anterior border of the lateral bone canthus.
Cataract due to lens damage was prevented using the
half beam technique (HBT).[,] When the HBT
is used in severe proptosis cases, extraocular muscles
and soft-tissue areas receive low doses, which leads to
a decrease in treatment success.[] Two lateral area techniques without half beam block (non-split beam
technique [NSBT]) were applied as an alternative to
the HBT. In NSBT, the lens and lacrimal glands were
exposed to high-dose radiation.[] With technology
development, 3D-CRT, a more effective technique for
better target volume coverage and preserving normal
tissues, has replaced this technique. Later, IMRT
emerged as an advanced RT technique that could better
dose distribution in irregular and complex structures
and began to take its place in orbital irradiation.
[] There are some reservations about its use in this
benign disease due to RT's side effects, which are used
as an alternative in cases resistant to steroid treatment.
Cataracts and secondary malignancies that may occur
due to RT are the main concerns. In the study of Bartalena
et al.,[] the incidence of cataracts was 10% in
patients who underwent orbital RT. The prevalence of
cataracts was higher, although not significantly compared
with the general population. No tumors were observed
in 157 patients submitted to CT scans of orbital
and adjacent regions. In the study of Wakelkamp et
al.,[] when RT (29%) and glucocorticoid groups(34%)
were compared, cataract development rates were found
to be similar. In addition, intracranial tumors were
not detected in any of the patients who received RT.
In summary, although a significant increase in serious
long-term adverse effects associated with RT has not
been reported in the literature.
RT decision should be made with caution in patients
with comorbidities that predispose to retinopathy,
such as hypertension and diabetes mellitus. In
our case, diabetes mellitus and hypertension developed
secondary to steroid treatment. However, in the
multidisciplinary council evaluation, it was decided
that RT would be appropriate for the patient because
it would take a long time to reach alternative treatment
options. In this patient, the retina and macula
were also contoured and there were no hotspots in
these areas (Fig. 2). The target tissue received the effective
dose and normal tissues such as the lens were
below the tolerance dose.
In a recent study evaluating the results of radiotherapy
using the IMRT technique in treating ophthalmopathy,
Li et al.[] reported the treatment results
of 178 patients. This study reported that patients
received a significant treatment response within 6
months after treatment. In cases whose symptom duration
is longer than 18 months and who continue to
smoke; it has been reported that RT has less treatment
success. In the case series, the rate of cataracts was
reported as 2.25%.
Dosimetric studies on the treatment of TO are also
available in the literature. Lee et al.[] reported the
dosimetric superiority of IMRT in their dosimetric
study, in which they evaluated ten patients diagnosed
with TO and receiving IMRT treatment. According
to their results, IMRT is significantly superior than
3DCRT and LOF and it provides better dose tolerance
in the globe, lenses, and optic nerves and has a
better conformity index and homogeneity index. In
the study by Nguyen et al.,[] in which seven patients
were evaluated retrospectively, Tomotherapy,
traditional HBT, and NSBT were compared dosimetrically.
Target dose administration was better in
tomotherapy; however, lens doses were higher than
others. Unlike this study, the lowest lens dose was obtained
with tomotherapy in our study. The reason for
this is that; there is a comparison with the 3D technique
in the study of Nguyen et al.;[] in our study,
different IMRT techniques were also compared. In
the study by Valentine et al.,[] HA, VMAT, and
2FPO (2-Area Parallel Opposite) techniques were
compared dosimetrically in TO. They obtained better
results with HA in critical organ doses, especially
lens and lacrimal gland doses. In our study, it was
aimed primarily to protect the lens doses. Ten Gy,
the dose limitation specified in the study of Emami et
al.,[] could not be achieved only in 3DCRT among
the techniques we compared.
Although the HA technique is a widely used method
for stereotactic radiosurgery in brain metastases, its
use has increased in other diseases as it provides better
dose distributions and critical organ doses[-] We
planned to use the HA technique to have a long life expectancy,
a better treatment plan and to minimize the
side effects of our patient.
Dosimetric and clinical trials using different and
modern techniques for better RT plans into treatment
are interesting research topics. In this case, we compared
HA and other IMRT techniques with conformal
RT in our clinic. In our study, frontal lobe doses were
also evaluated considering the patient"s age. Dose limitations
were generally provided with the HA technique
outside of this area. However, the clinical significance
of the higher dose distribution observed in the frontal
lobe is unknown.
RT is an important treatment option for the treatment
of steroid-resistant TO. In the treatment of this
benign disease, there is a need for dosimetric and
clinical studies comparing modern RT techniques to
apply the effective dose to the target area with minimum
side effects.
