Introduction
The goal of radiotherapy (RT) is to eradicate
tumor cells in the target volume, while sparing surrounding
organs at risk. Local or/and regional recurrence
is correlated to overall survival in many
tumor sites.[,] Although there is a relationship between
tumor dose and tumor control probability,
it’s difficult to prescribe high doses because of especially
late side effects of normal tissues. Organs
at risk could be protected and target volume doses
could be escalated with the improvement of patient
stabilization systems and 3D CRT techniques. RT
treatment delivery in head and neck tumors require
highly accurate and reproducible treatment set-up
due to many important organs at risk with confirmation
by frequent portal imaging.[] Organ motion
in the head and neck region is generally unimportant
and could be neglected except motions due to
swallowing. However, set-up errors could make a
significant difference for the doses planned to be
delivered to the target volume and to organs at risk.
These errors are classified as systematic and random
which are contained in the Planning Target
Volume (PTV) margins.
Nowadays margins to be added to have an adequate
PTV is of major concern for departments
where the 2D to 3D transition is taking place. With
3D conformation therapy, the volume of organs at
risk being irradiated is reduced. Set-up errors can be
measured using portal imaging by applying Electronic
Portal Imaging (EPI) instead of megavoltage
portal films taken during the RT. Over the last several
years, EPIs have become available in a large number
of institutions to measure the set-up errors.[,]
The aim of this study was to evaluate the set-up
errors using EPI to form a basis for the 3D CRT
protocol for the head and neck cancer treatment
protocol to be used in DEUDRO.
Methods
Patients: Between July 2004 - September 2005
10 patients who were planned to be treated with 3D
CRT MLC for head and cancer and who had suitable
bony landmarks in their EPI’s were evaluated.
Radiotherapy Technique
Immobilisation: Thermoplastic casts with two
point stabilisation of the head were used to immobilise all patients in suitable anatomic positions.
Proper neck supports were chosen by considering
the primary tumor localization for the patient lying
in supine position, but any shoulder immobilisation
hasn’t been used.
Computed Thomography (CT) simulation:
The upper and lower limits of the anatomic field
and slice interval were determined by the responsible
physician, and was marked on the individual
patient. Slice thickness was 3-5 mm. The mask of
the patient was marked with radioopac labels with
the help of laser beams.
Virtual simulation: The 3D conformal treatment
plan was performed in consistency with
ICRU (International Commitee of Radiation Units
and measurements) 50 and ICRU 62 guidelines.[4-6]
The findings on clinical examination and CT and/
or MRI before RT were used to constitute the GTV
(Gross Tumor Volume), the CTV (Clinical Target
Volume) and the PTV (Planning Target Volume).
[-] Planning volumes were consulted with the radiology
specialist in the complicated patients where
the volumes were not very clear. GTV tumor delineation
was done to include the primary tumor and
GTV node consisted gross lymphatic metastasis.
CTV (tumor and node) volumes were constructed
by addingmargins to GTV volumes as to clinical
protocols and experiences for probable microscopic
extension of disease. PTV volumes were planned
by adding 0.5 cm to the CTV, for possible set-up
errors. Internal margin has been neglected in this
study. The organ motion was insignificant because
of tumor localization in our head and neck cancer
patient in comparison with the other tumor sites.
Radiotherapy Dose and Energy: RT was
given 1.8-2 Gy per fraction, 5 days a week, 25-35
fractions to a total dose of 60-70 Gy The patients
were treated with high energy photons (6MVX).
Spinal cord was protected after 44-46 Gy using
with MLC at lateral fields. The dose planned for
the posterior servical lymphatics is completed by
6-9 MeVé electron energies.
EPI Evaluation Protocol
The DRR (Digitally Reconstructed Radiographs)
images of the treatment fields were used as references. The DRR s were imported from the
Treatment Planning to the treatment machine and
were compared on the screen with the EPI protocol
as mentioned below:
Frequency of the EPI: We aimed to evaluate
7 EPI images for each patient two during the first
week and one on each of the following 5 weeks .
Reference bony landmarks for the comparison
of the EPI: Lateral (L) image: base of the
skull, body and spina of C2 vertebra and the other
visible bony structures,
Anterioposterior (AP) image: nasal septum,
maxillar sinus, base of posterior skull, vertebras.
Evaluation of the EPI: Evaluation protocol
was an offline procedure. Images were evaluated
by two observers at the same day independently.
Siemens Primus Beamview TI® programme has
been used for EPI evaluation. Reference Digitally
Reconstructed Radiography (DRR) images were
compared to the EPI and the differences between
the EPI and the DRR using bony landmarks were
measured in cranio-caudal (CC), anterior-posterior
(AP) and medio-lateral (ML) directions. If the
difference in the measurements between the two
observers was smaller than 3 mm, the larger measurement
was taken into account. However if the
difference was larger than 3 mm than the mean of
the two measurements was taken.[]
EPI and Statistical analysis: Standard deviations
were calculated using an easy excel programme
prepared at Holland National Cancer Institute.
This programme calculates the mean, median
values and standard deviations. The random (σ) and
the systematic (Σ) components of the errors were
calculated using margin formula (2.5 x Σ + 0.7 x
σ) proposed by Van Herk to find out the planning
target volume (PTV) margin.[,] For each individual
patient, the random displacement for a particular direction
was assessed by the substraction of the systematic
displacement from the daily displacement.
For all patients, the distribution of random displacements
was expressed by the standart deviation (SD)
from all individual random values. Random, systematic
and total standart deviations are related by
the formula S2
TD = S2
SD + S2
RD where TD, SD and RD are total, systematic and random displacements,
respectively.[8] From the displacements measured in
each direction, 3- dimentional (3D) vector was calculated
using the formula d3D = √ d2
AP + d2
CC + d2
ML
where dAP, dCC and dML are the deviations in AP, CC
and ML directions, respectively.[]
Results
Patients: There were 6 (60%) male, and 4
(40%) female patients. The median age was 58 (33-
76). Tumor localizations were as follows: 6 (60%)
nasopharynx, 2 (20%) unknown primary with neck
nodes, 1 (10%) hypopharynx and 1 (10%) tonsil.
Patient characteristics are shown in Table 1.
Table 1: Patient characteristics
Results of EPI evaluation: Ninety three EPI’s
from 30 fields have been evaluated and 186 measurements
have been performed per observer. Total
number of measurements were 372. Ninety three
(50%) measurements were in CC, 78 (42%) were
in AP and 15 (8%) were in ML directions. Ninety
three EPI’s were suitable for measurement in terms
of bony landmarks and are evaluated in this study.
Larger than 3 mm values between the observers
have been determined in 28 (15%) measurements
[median 3.75 (3.01-9.14) mm].
Random error (σ) was found to be 2.6 mm for
AP, 2.9 mm for CC and 1 mm for, ML. Systematic error (Σ) was found to be 3.9 mm for AP, 1.8
mm for CC and 1.9 mm for ML. These data have
been used in the margin formula and margins to be added for PTV have been found to be AP: 11.7
mm, CC: 6.6 mm and ML: 5.8 mm. Results of EPI
evaluation are shown in Table 2 and total standart
deviations for each direction and calculated 3D
vectors are shown in Table 3.
Table 2: Results of EPI evaluation
Table 3: Total standart deviations for each direction and 3D vector
Distribution of the random displacements along
the 3 directions (AP, CC, ML) at all measuments
(Fig. 1), and scatter plot of the systematic set-up
displacement along the two directions (AP-CC)
(Fig. 2) are shown in figures.
Fig 1: Distribution of the random displacements along the 3 directions.
Fig 2: Scatter plot of the systematic set-up displacement
along the two directions (AP-CC). Each dot represent
the individual systematic displacement along the
specified direction. The mean value (M) represents
the average displacements for all patients.
Discussion
RT of head and neck cancer has difficulties because
of the organs at risk in vicinity of the tumor
a high geometrical accuracy is required. Set-up uncertainties
include not only the PTV, but also organ
motions. Organ motions can be neglected for
head and neck tumors.[,,] Hence margins added
for the PTV requires set-up reliability in particular
for new users of 3D CRT. Consequently RT fields
should be verified by means of portal imaging. The literature showed that, using portal imaging to
evaluate the set-up errors is very important during
the RT.[-] EPI is useful for easy repeated imaging,
processing, and rapid assessment of set-up errors
comparing with conventional portal images.
[,] Correction protocols have been recommended
for reduction of set-up deviations in many trials.
[,,-]
In this study, we purposed to determine our
margins for PTV for 3D RT and prepared an offline
correcting protocol for set-up errors in head
and neck cancer. Ten consecutive head neck cancer
patients were evaluated. RT was given 1.8-2 Gy
per fraction, 5 days a week, 25-35 fractions to a total
dose of 60-70 Gy with 6MVX. Spinal cord was
protected after 44-46 Gy using with MLC at lateral
fields. The posterior servical lymphatic’s dose was
completed by 6-9 MeVé electron. Offline correction
has been used in de Boer et al.’s and in many
studies.[-,]
Margins to be added to CTV to obtain PTV is
5-10 mm for RT of head and neck cancer in DEUDRO
- 3D CRT Protocol. It’s similar with other
studies[,] although there are differences between tumor localization, organs at risk volume, RT indication
(adjuvant/ radical) and immobilisation
systems.[,] Especially immobilisation is a very
important factor during the course of RT.[,,,]
The patients’ motions in the mask maybe increased
due to the weight lose, the wearing mask during the
RT. Many studies report on patient’s immobilisation
and describe different head and neck support
system. In van Lin et al.’s study, two mask systems
(standart versus customised head and neck support)
have been compared. Set-up errors has been
decreased with personalised equipment including
neck support.[] Willner et al. used dental bite
block and non-customised neck support system for
immobilisation.[] Systematic errors are similar
with our study. In Gilbeau et al.’s study, set-up errors
in immobilisation from 3 fields were bigger
than immobilisation from 4-5 fields.[] Mitine et al.
found larger systematic errors and much smaller
random error values for head and neck patients immobilised
in plastic masks.[] They conclued that,
set-up correction desicions based on a first-day
image is an effective procedure, because the large
systematic errors could be found with relatively
high accuracy from such a single image. Not only
set-up accuracy but also comfort level of patients,
set-up time[] and cost effectivity[] are very important
topics to decide choosing immobilisation
system. Weltens et al. compared a plastic PVC cast
and a thermoplastic cast and used a standart head
and neck support.[] They used EPI and magavoltage
portal films and measured the set-up errors in
craniocaudal (CC) and anterioposterior (AP) directions.
Even systematic AP errors are similar, and
CC measurements are better in our study. Thermoplastic
head-and-shoulder mask system was
compared with only head immobilisation mask in
Rotondo et al’s study. There were no significant
differences between two systems about set-up accuracy.[] Donato et al. assessed the cost of two different
head and neck immobilization systems, and
discussed that while displacements were slightly
equal but one system of them was more expensive.
[] In our study orfit masks and personalised neck
supports have been used.
In this study 210 EPI’s have been planned to be
measured, however only 93 have been evaluated. The most frequent cause of this underachievement
was high routine workload. The other causes were
imaging and recording errors due to radiotherapy
technicans Evaluation of the lower neck fields in
the EPI’s were very difficult because of the difficulty
in finding reference bony landmarks. Seven
EPI’s for each field has been planned but only 3-7
EPI’s were evaluated as in with some other studies.
[,] Two observers have measured all EPI’s in our
study. Two observers have measured 186 points
from 93 EPI’s and interobserver variation were
smaller than 3 mm in 85%. In Perera et al.’s trial
this is smaller than 5 mm.[] The variation between
observers may decrease, if reference points are described
very clearly.
Set-up errors (Table 2) and total standart deviations
for each directions (Table 3) have been
calculated. Systematic component of set-up error
(Σ) in AP and STDAP was found larger than the
other measurements. These influenced the “Margin”
formula, and margin added to the PTV in
AP direction. The distribution of the random displacements
(Fig. 1) and scatter plot of systematic
set-up displacement about AP-CC directions (Fig.
2) are shown that similar cumulative deviation as
about 3 mm. So, in clinics which new user of the
3D CRT should be very careful while choosing the
margin each directions. In Suzuki et al.’s study, the
intrafractional organ motions and the interfractional
set-up errors were analyzed for head and neck
IMRT. The organ motions were determined as to coordinates of the landmarks on the image. The
set-up errors were defined as to bony landmarks on
the portal imaging, and they adopted a PTV-margin
of 5mm and a PRV-margin of 3mm for head and
neck IMRT.[]
Set-up errors and accepted margins from different
studies are shown in Table 4.
Table 4: Set-up errors and accepted margins from different studies
Conclusion
Margins to be added for PTV have been found
to be AP: 11.7 mm, CC: 6.6 mm ve ML: 5.8 mm in
this study. Margins shoul not be equal in 3 directions.
Set-up errors could be diminished with better
immobilisation systems including the shoulders,
education of the team, using spesific protocols and
reporting the measurement data for different tumor
localization. Conformal radiotherapy must be performed
under optimal conditions and adequate experiences
especially in new centers.
This study includes the head and neck cancer
patients treated between July 2004-September
2005 in DEUDRO. These margins might be wide
especially for IMRT, so nowadays PTV margins
are efforted to reduce with better immobilization
systems.
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