Radiotherapy and Oncology xxx (2018) xxx–xxx

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Radiotherapy and Oncology

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Original article

Total-body irradiation using linac-based volumetric modulated arc

therapy: Its clinical accuracy, feasibility and reliability
Bora Tas a,⇑, Ismail Faruk Durmus a, Ayse Okumus a, Omer Erol Uzel a, Muge Gokce b, Hasan Sami Goksoy b,
Esat Mahmut Ozsahin c
a
Department of Radiation Oncology; b Department of Hematology, Yeni Yuzyil University Gaziosmanpasa Hospital, Istanbul, Turkey; c Department of Radiation Oncology, Centre
Hospitalier Universitaire Vaudois, Lausanne, Switzerland

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: To report the feasibility, accuracy, and reliability of volumetric modulated arc therapy (VMAT)-
Received 12 March 2018 based total-body irradiation (TBI) treatment in patients with acute myeloid leukemia (AML) or acute lym-
Received in revised form 2 August 2018 phoblastic leukemia (ALL).
Accepted 3 August 2018
Materials and methods: From 2015 to 2018, 30 patients with AML or ALL were planned and treated with
Available online xxxx
VMAT-based TBI, which consisted of three isocenters and three overlapping arcs. TBI dose was prescribed
to 90% of the planning treatment volume (PTV) receiving 12 Gy in six fractions, at two fractions per day.
Keywords:
Mean lung and kidney doses were restricted less than 10 Gy, and maximum lens dose less than 6 Gy.
DVH-based 3D patient QA
VMAT
Quality assurance (QA) comprised the verification of the irradiation plans via dose–volume histogram
TBI (DVH) based 3D patient QA system.
Results: Average mean lung dose was 9.7 ± 0.2 Gy, mean kidney dose 9.6 ± 0.2 Gy, maximum lens dose
4.5 ± 0.4 Gy, mean PTV dose 12.7 ± 0.1 Gy, and heterogeneity index of PTV was 1.16 ± 0.02 in all patients.
Grade 3 or more acute radiation toxicity was not observed. When comparing plan and DVH-based 3D
patient QA results, average differences of 3.3% ± 1.3 in mean kidney doses, 1.1% ± 0.7 in mean lung doses,
and 0.9% ± 0.4 in mean target doses were observed.
Conclusion: Linac-based VMAT increased the dose homogeneity of TBI treatment more than extended
SSD techniques. Partial cone-beam CT and optical surface-guided system assure patient positioning.
DVH-based 3D patient dose verification QA was possible with linac-based VMAT showing small differ-
ences between planned and delivered doses. It is feasible, accurate, and reliable.
Ó 2018 Elsevier B.V. All rights reserved. Radiotherapy and Oncology xxx (2018) xxx–xxx

Radiation therapy (RT) in the form of total-body irradiation and Marrow Transplantation (EBMT) [6], which suggest to check
(TBI) technique continues to be an important part of conditioning the dose homogeneity along the patient’s midline at several points
regimens in patients undergoing bone-marrow transplantation and to specify the lung dose at a point, which is representative for
(BMT) in hematological malignancies. TBI implemented using more than 50% of the lung volume. Most of the current TBI proce-
megavoltage photon beams is a conditioning modality used in dures are based on techniques established on linear accelerators
treating several diseases, including multiple myeloma, leukemias, used for conventional RT. Large photon fields are generally
lymphomas, and some solid tumors [1,2]. Studies in mice and achieved by treating the patient at extended skin-surface distance
humans show that the toxicities of TBI can be improved further (SSD) with standard linear accelerators or with special dedicated
by fractionating the radiation dose [3,4]. A randomized study from machines. Equipment Guidelines recommend the use of parallel-
Seattle in the setting of AML compared single-dose TBI (10 Gy) to a opposed pairs of high-energy photon beams from 4 to 18 MV for
fractionated schedule (12 Gy in 6 fractions). The last update of this TBI [2]. Classic TBI has a long application time, non-conformality
trial showed significant superiority of the fractionated scheme in of beam-application with the inability to individually spare organs
terms of event-free survival [5]. Most of the current methods at risk (OARs) and hence, its acute and late toxicity [7–11]. The use
follow the recommendations of the European Group for Blood of an inverse optimization algorithm improves the dose homo-
geneity in comparison to conventional forward planned tech-
niques. The large target size hampers the use of modern methods
⇑ Corresponding author at: Department of Radiation Oncology, Yeni Yuzyil
for linear accelerator of radiation oncology.
University Gaziosmanpasa Hospital, Merkez mah Cukurcesme cad No: 51, Gazios-
manpasa, 34245 Istanbul, Turkey.
Individually implemented RT improves the dose distribution on
E-mail address: [email protected] (B. Tas). target structures and organs at risk (OAR) more than extended SSD

https://doi.org/10.1016/j.radonc.2018.08.005
0167-8140/Ó 2018 Elsevier B.V. All rights reserved.

Please cite this article in press as: Tas B et al. Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility
and reliability. Radiother Oncol (2018), https://doi.org/10.1016/j.radonc.2018.08.005
2 Total-body irradiation using VMAT

techniques. Using volumetric modulated arc therapy (VMAT) Gaziosmanpasa Hospital in Istanbul from 2015 to 2018. Patient
delivery, one can increase both conformality and homogeneity in age ranged from 6 to 63 years with a mean and median age of
target-dose distribution. VMAT functionality can optimize single 21.5 and 18.5 years, respectively. TBI prescription dose was set in
or multiple coplanar or non-coplanar arcs simultaneously, provid- such a manner that 90% of the clinical target volume (the whole
ing the flexibility and control needed for more complex treatment body) received 12 Gy in six fractions, at two fractions per day;
plans. Using VMAT for TBI, we strived for individual control over mean doses to lungs and kidneys were restricted less than 10 Gy,
dose distribution for optimal target coverage and highly conformal and maximum dose to lens were restricted less than 6 Gy.
sparing of OAR such as the lungs at the same time to possibly Heterogeneity index was calculated as: D5 (minimum dose in
decrease acute and late treatment sequelae. Target dose coverage 5% of the target, ‘‘indicating the maximum dose”) divided by D95
and OAR doses also depend significantly on VMAT techniques, (minimum dose in 95% of the target, ‘‘indicating the minimum
which are single-arc, dual-arc, and 2-field VMAT for each isocenter. dose”).
Multi-leaf collimator (MLC) mostly moves just one side of isocenter
in first tour of VMAT then, with the dual-arc technique, it moves to
other side of isocenter in second tour of VMAT; therefore, dual-arc Immobilization and planning CT
VMAT technique decreases monitor units (MU) and delivery time
Patients were immobilized in supine position using customized
of treatment. Moreover, a benefit could be demonstrated with
thermoplastic masks for head support and a vacuum cushion
regard to dose distribution and homogeneity and dose-reduction
(Elekta BlueBAGTM, Henderson, NV) for body support on an adjus-
to OAR using Monaco 5.1Ò treatment planning system (TPS) [12].
table (Elekta ProSTEPTM, Henderson, NV) board (Fig. 1).
To check the accuracy of dose calculations and mechanical
In case of patients taller than 120 cm in body length, two com-
issues of RT treatment planning, each intensity-modulated treat-
puted tomography (CT) data sets were acquired using Biograph
ment plan requires dose verification before the treatment delivery
mCT (Siemens Medical Solutions, USA). One of them is head-first
to the patient. Currently, each individual plan is calculated in a
scan from vertex to lower thigh, and the other one feet-first scan
phantom geometry and delivered to the phantom. The dose is then
from toes to upper thigh, because of limited couch motion capaci-
measured using ion chambers and radiographic or radiochromic
ties of the linear accelerator (Fig. 2).
films, or with detector arrays alone [13,14]. The calculated dose
is then compared with the measured dose.
Possible method of verifying dose distribution is to use 2D or 3D
detector arrays. Although these have dramatically speeded up
IMRT dose verification, commercially available arrays are not suit-
able for TBI because of their limited array size requiring multiple
quality assurance (QA) delivery. Furthermore, the electronic circuit
of a 2D or 3D array will be irradiated in TBI delivery, resulting in
damage to the detector array.
In our study, the QA comprised the verification of the irradia-
tion plans via DVH-based 3D patient QA system.
Here, we present our linac-based VMAT TBI technique at nom-
inal skin-axis distance (SAD) technique on the couch.

Materials and methods

Patient criteria and dose prescription

Thirty patients (19 male, 11 female) with AML or ALL under-
went allogenic stem-cell transplantation following TBI treatment
with linac-based VMAT technique at Yeni Yuzyil University Fig. 2. Registration of head-first and feet-first CT sets.

Fig. 1. Immobilization of (a) pediatric patient and (b) adult patient.

Please cite this article in press as: Tas B et al. Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility
and reliability. Radiother Oncol (2018), https://doi.org/10.1016/j.radonc.2018.08.005
 B. Tas et al. / Radiotherapy and Oncology xxx (2018) xxx–xxx 3

Contouring 5.11Ò TPS. Plan adaptation delivery while ensuring OAR tolerances
never exceeded due to bias-dose planning because TPS considers
Contouring was performed using Prosoma 4.0Ò (Medco,
dose distribution from previous plans while optimizing the cumu-
Germany) contouring work station. The following structures were
lative dose distribution.
created: outer body contour, lungs, kidneys, lens, couch, vacuum
cushion, prostep, head step, pillow, and planning target volume
(PTV) consisted of whole body without skin (3-mm distance to Patient setup verification
the surface, lungs, kidneys, and lens).
XVI 5.0 partial kV cone-beam CT (CBCT) was used as an image-
guided RT (IGRT) method for each VMAT delivery. SentinelÒ or
Treatment planning CatalystÒ (C-RAD AB, Sweden) laser-based optical surface-guided
devices were used for patient positioning and intra-fraction motion
TBI was implemented using Versa HDTM (Elekta AB, Sweden) detection (Fig. 3).
linear accelerator with AgilityÒ (Elekta AB, Sweden) collimator Average total duration of one fraction linac-based VMAT tech-
system. This collimator system included 160-leaf MLC, minimum nique treatment, including patient positioning, IGRT and beam
leaf width being 5 mm, and maximum field size 40  40 cm2 at on time, was 55 ± 5 min for an adult patient and 35 ± 4 min for
nominal SAD at 100 cm. pediatric patients in our clinic.
Dual-arc VMAT plans were generated on Monaco 5.11Ò (Elekta
AB, Sweden) TPS. Monaco has the XVMC Monte Carlo dose engine,
Quality assurance
for electron and photon, for continuous arc calculation as a single
beam, rather than just dose approximations that occur with many For the purpose of QA, two different procedures of dosimetry
discrete (control point) gantry angle positions. Nominal variable were applied for each patient’s treatment plans. One of them is
dose rate was adjusted to obtain a mean dose rate of 250 MU/ the QA comprising the verification of the irradiation plans via
min (range 50–600 MU/min) during treatment as a phase III DVH-based 3D patient QA system, which was DolphinÒ and Com-
prospective randomized study has already reported that instanta- passÒ, between plans and delivered doses. DolphinÒ transmission
neous dose rate influences neither the outcome nor the toxicity detector has 1513 air-vented plain parallel ionization chambers
when TBI dose is fractionated [15]. Mean instantaneous dose rate of 3.2 mm (Ø)  2.0 mm (h); chamber volume 0.016 cm3, 5.0 mm
was 30 ± 6 cGy/min. Calculation parameters were grid spacing spacing in central area, and it has 40  40 cm2 treatment field-
0.4 cm, minimum segment width 0.5 cm, maximum 180 control size coverage. DolphinÒ was attached to the gantry wirelessly to
points per arc, fluence-smoothing medium, statistical uncertainty operate, therefore no cables were needed to assure an excellent
1.0% per calculation, gantry increment of 30°, and calculate dose setup positioning accuracy. Basically, the aim of this detector
deposition to medium. MLC’s effective speed was 6.5 cm/s, and leaf system is to reconstruct the dose into the patient CT, injecting
travel was 15 cm over the central axis. delivered fluence instead of the calculated one from the TPS model
The VMAT-TBI technique consisted of three isocenters and three software. We evaluated the plan in the patient CT based on gamma
overlapping arcs. Overlapping arcs had junctions’ region between and DVH metrics with CompassÒ software, which has an indepen-
each two fixed-field sizes up to 2.0 cm, and treatment planning dent TPS integrated Collapsed-Cone algorithm. Then, each treat-
system considered junction region during the optimization pro- ment plan was re-calculated with 3.0-mm, 6.0-mm, 9.0-mm, and
cess; therefore, we prevented from double dose in the junction 12.0-mm longitudinal misalignment of second and third overlap-
region related with misalignment while using overlapping arcs in ping arcs to check the reliability of the treatment by Monte Carlo
the same optimisation. Linac-based VMAT can treat targets up to algorithm.
120 cm length on the couch for head first CT sets, because of lim-
ited couch motion capacity of the linac. One or two more overlap-
Toxicity assessment
ping arcs were added, depending on the height of the patient for
feet first CT sets. High-dose junction regions were eliminated after Treatment-related toxicity was assessed according to the
the registration of two CT sets via bias-dose properties of Monaco Common Terminology Criteria for Adverse Events (CTCAE v 4.03).

Fig. 3. TBI patient positioning and monitoring by SentinelÒ laser-based optical surface-guided system.

Please cite this article in press as: Tas B et al. Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility
and reliability. Radiother Oncol (2018), https://doi.org/10.1016/j.radonc.2018.08.005
4 Total-body irradiation using VMAT

In general, diarrhea and/or oral mucositis necessitating total par- dose was 12.7 ± 0.1 Gy, and heterogeneity index (HI) of PTV was
enteral nutrition was considered as grade 3 toxicity. 1.16 ± 0.02 in 30 patients (Table 1). Dose distribution of TBI treat-
ment is shown in Fig. 4. Mean and median follow-up times were 16
Results and 18 months.
Overall TBI-induced acute toxicity (CTCAE v 4.03) was low with
Average mean lung dose was 9.7 ± 0.2 Gy, mean kidney dose only grade 1 and 2 morbidity: patchy mucositis in 16 (62%), nausea
was 9.6 ± 0.2 Gy, maximum lens dose was 4.5 ± 0.4 Gy, mean PTV not requiring antiemetics in 12 (46%), headache in 11 (42%), fatigue
in 9 (35%), neck pain in 8 (31%), xerostomia in 7 (27%), loss of appe-
Table 1 tite in 6 (23%), and faint or dull erythema in 4 (15%) patients
Dosimetric features of TBI by dual-arc VMAT technique. (Table 2). Grade 3 and more acute radiation toxicity was not
observed. All patients are still alive, and no leukemia relapse was
Patient Mean Mean Max. lens PTV mean HI
number lungs (Gy) kidneys (Gy) (Gy) (Gy) observed.
When comparing plan and DVH-based 3D patient QA results
1 9.84 9.45 4.32 12.47 1.17
2 9.75 9.62 3.86 12.65 1.16 (see Fig. 5), we determined average differences of 3.3% ± 1.3 mean
3 9.23 9.21 4.57 12.67 1.15 kidney doses, 1.1% ± 0.7 mean lung doses, 0.9% ± 0.4 mean target
4 9.73 9.78 4.87 12.66 1.12 doses, and an average PTV c index of 0.39 ± 0.07 was observed
5 9.88 9.93 5.12 12.77 1.18 for 3%-3 mm analysis (Table 3).
6 9.85 9.58 4.78 12.64 1.15
When plans were recalculated with longitudinal misalign-
7 9.68 9.68 4.87 12.91 1.21
8 9.97 9.94 3.81 12.43 1.15 ments, an average of 2.0% ± 0.7, 3.7% ± 1.2, 6.5% ± 1.7 and
9 9.71 9.70 3.63 12.82 1.20 7.2% ± 1.7 higher mean lung doses; 2.6% ± 1.5, 9.9% ± 3.7,
10 9.75 9.62 4.41 12.54 1.12 15.1% ± 4.2 and 22.6% ± 3.1 higher maximum lung doses and
11 9.55 9.84 4.42 12.72 1.16
3.6% ± 1.3, 11.9% ± 3.2, 20.4% ± 3.6 and 22.0% ± 3.8 higher point
12 9.56 9.57 4.21 12.90 1.14
13 9.53 9.31 4.42 12.64 1.15
doses were obtained respectively; with each 3.0-mm, 6.0-mm,
14 9.95 9.54 5.25 12.77 1.18 9.0-mm, and 12.0-mm longitudinal misalignments (Table 4 and
15 9.87 9.81 4.39 12.89 1.21 Fig. 6).
16 9.63 9.54 4.65 12.51 1.14
17 9.82 9.73 4.11 12.80 1.15
18 9.60 9.65 4.97 12.65 1.18
19 9.65 9.75 4.80 12.57 1.15
20 9.75 9.52 4.56 12.62 1.18 Table 2
21 9.84 9.66 4.82 12.74 1.15 Acute radiation morbidity.
22 9.86 9.68 4.61 12.59 1.17
23 9.72 9.62 4.42 12.64 1.16 Grade 1 and 2 acute toxicity Number of patients (%)
24 9.65 9.60 4.85 12.60 1.17
Patchy mucositis 16 (62)
25 9.63 9.63 4.66 12.84 1.15
Fatigue 9 (35)
26 9.69 9.54 4.82 12.72 1.16
Loss of appetite 6 (23)
27 9.60 9.52 4.20 12.62 1.17
Xerostomia 7 (27)
28 9.65 9.56 4.42 12.68 1.17
Faint or dull erythema 4 (15)
29 9.72 9.64 4.84 12.58 1.16
Nausea not requiring antiemetics 12 (46)
30 9.42 9.38 4.62 12.60 1.17
Headache 11 (42)
Mean ± SD 9.70 ± 0.16 9.62 ± 0.16 4.54 ± 0.38 12.67 ± 0.12 1.16 ± 0.02
Neck pain 8 (31)
PTV: planning treatment volume; HI: heterogeneity index; SD: standard deviation.

Fig. 4. TBI dose distribution in sagittal, coronal, and axial planes by dual-arc VMAT technique.

Please cite this article in press as: Tas B et al. Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility
and reliability. Radiother Oncol (2018), https://doi.org/10.1016/j.radonc.2018.08.005
 B. Tas et al. / Radiotherapy and Oncology xxx (2018) xxx–xxx 5

Fig. 5. Dosimetric comparison between planned and delivered doses using DVH-based 3D patient QA system.

Discussion technique using the helical TomotherapyÒ system (HT; Accuray

Inc., USA) [16–18]. Dose homogeneity in the target and dose differ-
The concept of linac-based VMAT for TBI offers higher dose con- ences in specific organs were also determined using the linac-
formality due to 360° of beam application than the standard fixed- based VMAT technique, and each system has its own advantages;
beam approach. The intensity-modulated TBI technique has the HT allows 145-cm table motion capacity, unlike linacs. On the
potential to homogenize dose distribution to target, and to reduce other hand, linac-based VMAT allows kV CBCT and optical
dose on specified organs; several studies demonstrated this kind of surface-guided therapy for high-accuracy positioning and intra-
fraction motion detection, unlike HT. Springer et al. and Symons
et al. performed TBI treatment with linac-based VMAT in seven
Table 3 patients and in five patients, respectively; they reported the bene-
DVH-based 3D patient QA results. fit of satisfactory dose distribution within the PTV using 9–15
Patient Mean lung Mean kidney Mean PTV Average isocenters for planning [19,20]. In our technique, we could reduce
number dose dose dose c-index of PTV the number of isocenters between 3 and 5 when using 40  40 cm2
difference (%) difference (%) difference (%) field-size overlapping dual arcs, therefore the total treatment dura-
1 0.3 3.6 0.6 0.38 tion was decreased. Furthermore, high or less dose distribution in
2 0.0 4.0 0.9 0.56 junction region between head-first and feet-first CT was elimi-
3 0.8 4.6 0.6 0.32 nated when using bias dose properties of Monte Carlo algorithm-
4 0.5 1.7 0.2 0.28
5 1.0 4.5 0.9 0.36
based Monaco 5.11Ò TPS.
6 1.3 3.1 0.3 0.42 Belkacemi et al. reported that the 10-year probability of esti-
7 1.7 6.7 0.4 0.52 mated cataract incidence was 43% after fractionated TBI, therefore,
8 0.1 4.4 0.4 0.38 we clinically decided to protect lens and kept the mean orbita-lens
9 0.3 2.0 1.0 0.36
dose at 9.0 Gy; we have not observed intra-ocular recurrence yet
10 1.7 7.2 0.7 0.42
11 0.8 2.4 1.4 0.36 [21]. However, lens protection may not be considered in case of
12 0.7 1.1 1.0 0.44 high risk retro-ocular relapse of leukemia, as a clinical decision.
13 1.2 1.6 1.0 0.38 Dose verification for TBI can be performed using various phan-
14 3.1 4.7 0.7 0.32 toms and detectors. Gruen et al. performed dose verification using
15 0.8 3.1 0.7 0.42
16 0.2 3.2 0.3 0.40
a cheese phantom for point-dose measurements with ion cham-
17 1.1 3.8 0.5 0.46 bers [17]. Hui et al. used a cylindrical phantom of 30-cm diameter
18 0.5 2.5 1.0 0.45 and 36-cm length [22]. Zhuang et al. used a Meditec solid water
19 0.8 3.0 1.0 0.49 phantom of 30 cm  30 cm  12 cm with a 0.6-cc PTV Farmer-
20 1.2 2.8 1.2 0.42
type ion chamber and EDR2 film [23]. None of these are long
21 1.4 3.3 1.4 0.28
22 1.8 2.4 1.4 0.34 enough to verify the large treatment lengths used in TBI.
23 1.2 3.2 0.9 0.36 Several groups have used thermoluminescent dosimeters in a
24 0.6 2.8 0.8 0.41 random phantom to verify doses for TBI allowing measurement
25 0.4 3.4 1.4 0.42 of point doses in the whole body in a single delivery of a TBI treat-
26 2.2 3.8 1.6 0.31
27 1.8 2.4 1.2 0.46
ment plan [17,24,25]. However, 2D-gamma passing rates have
28 2.0 2.6 1.0 0.42 shown a poor correlation with critical DVH errors in anatomical
29 1.6 2.4 1.4 0.38 regions of interest [26,27]. There is a need to verify full 3D dose
30 1.2 2.2 1.6 0.30 distribution on a patient anatomy in order to make per-patient
Mean ± SD 1.1%±0.7 3.3%±1.3 0.9%±0.4 0.39 ± 0.07
QA more sensitive and specific. In our study, we measured
PTV: planning treatment volume; SD: standard deviation. 40  40 cm2 full treatment field size using DolphinÒ detector,

Please cite this article in press as: Tas B et al. Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility
and reliability. Radiother Oncol (2018), https://doi.org/10.1016/j.radonc.2018.08.005
6 Total-body irradiation using VMAT

Table 4
Deviation of longitudinal misalignment.

3-mm misalignment 6-mm misalignment 9-mm misalignment 12-mm misalignment

Patient Lung Lung Max. PTV Max. Lung Lung PTV Max. Lung Lung PTV Max. Lung Lung PTV Max.
number Mean (%) (%) (%) Mean (%) Max. (%) (%) Mean (%) Max. (%) (%) Mean (%) Max. (%) (%)
1 2.4 2.0 3.5 5.1 8.8 10.9 8.5 20.5 22.1 7.6 18.6 17.5
2 1.1 2.0 3.9 2.9 11.1 8.1 4.5 18.5 16.5 8.4 20.4 19.2
3 0.9 1.2 2.4 4.6 9.6 12.9 7.1 18.9 19.4 5.5 24.6 18.6
4 0.8 0.8 4.6 1.1 4.6 11.2 3.6 9.7 20.9 5.8 28.4 26.8
5 2.6 5.6 1.2 5.2 16.4 10.8 8.2 21.2 22.5 4.8 19.4 22.1
6 3.1 5.8 5.8 1.2 18.9 18.9 10.1 19.6 29.4 9.4 28.6 21.6
7 0.8 0.9 4.5 1.1 4.6 11.2 3.8 9.6 20.8 5.2 22.5 19.3
8 2.5 2.3 6.7 5.0 5.5 19.2 3.8 10.9 25.7 6.8 21.3 18.6
9 1.2 2.2 2.2 2.4 13.0 13.9 3.8 17.5 18.4 8.6 19.8 22.4
10 1.8 5.7 2.0 4.5 14.5 10.5 7.0 20.2 16.5 8.4 22.4 20.5
11 1.6 4.4 2.4 3.3 15.8 11.2 5.2 25.4 16.8 8.2 26.3 28.2
12 2.5 5.0 3.3 5.0 9.5 12.9 7.8 13.8 19.3 7.6 24.8 27.5
13 2.4 1.7 1.1 4.5 5.4 4.8 6.8 9.4 14.6 5.2 22.3 23.5
14 2.0 2.6 5.9 4.0 9.5 8.9 6.1 17.0 15.8 4.9 18.8 16.8
15 2.4 1.0 3.2 4.9 8.1 7.9 7.2 11.5 17.5 10.2 19.6 18.6
16 2.0 0.9 4.9 4.7 7.0 15.8 8.4 22.5 25.5 9.2 20.4 19.2
17 1.4 0.8 1.8 2.6 16.5 7.4 6.4 14.0 16.4 8.6 21.5 19.8
18 3.4 0.8 4.0 3.6 7.5 11.5 4.0 11.5 19.0 6.7 22.7 24.6
19 2.2 1.8 4.4 2.6 6.4 12.2 6.8 14.6 20.4 5.4 22.3 23.1
20 1.6 2.8 4.2 3.6 6.8 10.5 7.2 12.4 18.8 6.2 21.4 22.4
21 1.8 3.6 4.7 2.8 7.6 6.8 6.4 14.8 22.4 5.6 20.5 26.6
22 2.7 3.8 3.6 4.4 8.8 14.6 7.8 16.4 26.7 5.3 20.3 21.5
23 2.6 2.4 3.2 4.0 9.2 12.5 8.6 12.6 16.8 9.0 23.7 19.4
24 1.4 2.1 3.8 3.6 6.6 13.6 6.4 11.8 19.6 6.7 32.0 20.7
25 2.6 2.4 2.9 4.0 11.5 14.2 6.8 13.2 22.4 10.9 25.4 33.6
26 2.2 2.5 3.8 3.8 12.2 13.4 7.2 10.8 25.6 5.6 22.6 19.0
27 2.2 4.2 3.8 4.8 9.4 10.8 5.6 14.6 18.6 6.6 19.8 26.2
28 1.8 2.8 4.4 4.2 12.4 14.6 4.8 10.8 19.4 8.4 23.8 22.4
29 1.6 3.4 2.8 3.8 10.6 14.4 8.4 12.8 20.6 7.0 20.6 18.8
30 2.6 1.8 4.2 3.0 8.8 12.0 7.4 16.0 22.4 7.4 22.5 20.6
Mean ± SD 2.0% ±0.7 2.6% ±1.5 3.6% ±1.3 3.7% ±1.2 9.9% ±3.7 11.9% 6.5% ±1.7 15.1% 20.4% 7.2% ±1.7 22.6% 22.0%
±3.2 ±4.2 ±3.6 ±3.1 ±3.8

PTV: planning treatment volume; SD: standard deviation.

Fig. 6. Prescribed-dose (95%) distribution of 3.0-mm, 6.0-mm, 9.0-mm, and 12.0-mm longitudinal misalignments.

and each air-vented plain parallel ionization chambers were homogeneity, high precision in patient positioning and dose deliv-
0.016 cc. Moreover, CompassÒ 3D verification software was cap- ery, less toxicity for specific OARs, and patient comfort could be
able to calculate overlapping arcs using independent dose calcula- achieved. Partial kV CBCT and optical surface-guided system
tion engine with delivered dose offering more informative QA assured patient positioning for accurate dose delivery. Moreover,
results. up to 6-mm longitudinal misalignment has not caused more than
Linac-based VMAT TBI has clear advantages compared to con- average 4.0% mean lung-dose enhancement while using overlap-
ventional methods making its use very attractive. Excellent dose ping dual-arc optimization and bias-dose properties of Monaco

Please cite this article in press as: Tas B et al. Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility
and reliability. Radiother Oncol (2018), https://doi.org/10.1016/j.radonc.2018.08.005
 B. Tas et al. / Radiotherapy and Oncology xxx (2018) xxx–xxx 7

5.11Ò TPS. DVH-based 3D patient dose verification QA was possi- [12] Tas B, Durmus IF, Okumus A, Uzel OE. Dosimetric evaluation of total body
irradiation (TBI) treatment by volumetric modulated arc therapy (VMAT) on
ble, showing small differences between planned and delivered
the couch. Biophys Biochem 2017;1(1):103.
doses. An average PTV c index <0.4 was observed for 3%-3-mm [13] Kron T, Yartsev S, Mackie T. Verification dosimetry during treatment for helical
analysis, showing highly precise dose distribution between tomotherapy using radiographic film. Australas Phys Eng Sci Med 2005;28
planned and delivered doses. Grade 3 and more acute radiation (4):232–7.
[14] Langen KM, Papanikolaou N, Balog J, Crilly R, Followill D, Goddu SM, et al. QA
toxicity was not observed. Thus, we conclude that VMAT-based for helical tomotherapy: report of the AAPM task group 148. Med Phys
TBI treatment on the couch is feasible, accurate, and reliable. 2010;37:4817.
[15] Ozsahin M, Pene F, Touboul E, Gindrey-Vie B, Dominique C, Lefkopoulos D,
et al. Total-body irradiation before bone marrow transplantation: Results of
Conflict of interest two randomized instantaneous dose rates in 157 patients. Cancer
1992;69:2853–65.
[16] Salz H, Bohrish B, Howitz S, Banz N, Weibert K, Wiezorek T, et al. Intensity-
None declared.
modulated total body irradiation (TBI) with TomoDirect. Radiat Oncol
2015;10:58.
References [17] Gruen A, Ebell W, Wlodarczyk W, Neumann O, Kuehl JS, Stromberger C, et al.
Total body irradiation (TBI) using helical tomotherapy in children and young
[1] Zheng Y, Dou Y, Duan L, et al. Using chemo-drugs or irradiation to break adults undergoing stem cell transplantation. Radiat Oncol 2013;8(1):92.
immune tolerance and facilitate immunotherapy in solid cancer. Cell Immunol [18] Penagar’cano JA, Chao M, Van Rhee F, Moros EG, Corry PM, Ratanatharathorn V.
2015;294(1):54–9. Clinical feasilibilty of TBI with helical tomotherapy. Bone Marrow Transplant
[2] Levitt, SH, Purdy JA, Perez CA, editors. Technical basis of radiation therapy: 2011;46(7):929–35.
practical clinical applications. Berlin, Germany: Springer, 2012;31:786–797. [19] Springer A, Hammer J, Winkler E, Track C, Huppert R, Böhm A, et al. Total body
[3] Travis EL. The sequence of histological changes in mouse lungs after single irradiation with volumetric modulated arc therapy: dosimetric data and first
doses of x-rays. Int J Radiat Oncol Biol Phys 1980;6(3):345–7. clinical experience. Radiat Oncol 2016;11(46):1–9.
[4] Vegesna V, Withers HR, Thames Jr HD, et al. Multifraction radiation response of [20] Symons K, Morrison C, Pary J, Woodings S, Zissiadis Y. Volumetric modulated
mouse lung. Int J Radiat Biol Relat Stud Phys Chem Med 1985;474:413–22. arc therapy for total body irradiation: a feasibility study using Pinaccle
[5] Thomas ED. Total body irradiation regimes for marrow grafting. Int J Radiat treatment planning system and Elekta Agility linac. J Appl Clin Med Phys.
Oncol Biol Phys 1990;19(5):1285–8. 2018:1–8.
[6] Sanchez-Doblado F, Quast U, Arrans R, Errazquin L, Sanchez-Nieto B, Terron JA. [21] Belkacemi Y, Labopin M, Vernant JP, et al. Cataracts after total body irradiation
Total body irradiation prior to bone marrow transplantation. Report of and bone marrow transplantation in patients with acute leukemia in complete
European Group for Blood and Marrow Transplantation. 1995, Sevilla. remission: a study of the European Group for Blood and Marrow
[7] Boelling T, Kreuziger DT, Ernst I, Elsayed H, Willich N. Retrospective, Transplantation. Int J Radiat Oncol Biol Phys 1998;41(3):659–68.
monocentric analysis of late effects after total body irradiation in adults. [22] Hui SK, Verneris M, Higgins P, Gerbi B, Weigel B, Baker S, et al. Helical
Strahlenther Onkol 2011;187:311–5. tomotherapy targeting total bone marrow: first clinical experience at the
[8] Linsenmeier C, Thoennessen D, Negretti L, Bourquin JP, Streller T, Lütolf UM, University of Minnesota. Acta Oncol 2007;46(2):250–5.
et al. Total body irradiation (TBI) in paediatric patients: a single center [23] Zhuang AH, Liu A, Schultheiss TE, Wong JYC. Dosimetric study and verification
experience after 30 years of low-dose rate irradiation. Strahlenther Onkol of total body irradiation using helical tomotherapy and its comparison to
2010;186:614–20. extended SSD technique. Med Dosim 2011;35(4):243–9.
[9] Gerstein J, Meyer A, Sykora KW, Frühauf J, Karstens JH, Bremer M. Long-term [24] Hui SK, Kapatoes J, Fowler J, Henderson D, Olivera G, Manon RR, et al.
renal toxicity in children following fractionated total-body-irradiation (TBI) Feasibility study of helical tomotherapy for total body or total marrow
before allogeneic stem cell transplantation (SCT). Strahlenther Onkol irradiation. Med Phys 2005;32:3214–24.
2009;185:751–5. [25] Surucu M, Yeginer M, Kavak GO, Fan J, Radosevich JA, Aydogan B. Verification
[10] Pommier P, Sunyach MP, Pasteuris C, Frappaz D, Carrie C. Second cancer after of dose distribution for volumetric modulated arc therapy total marrow
total-body irradiation (TBI) in childhood. Strahlenther Onkol 2009;185 irradiation in a humanlike phantom. Med Phys 2012;39(1):281.
(2):13–6. [26] Nelms BE, Zhen H, Tomé WA. Per-beam, planar IMRT QA passing rates do not
[11] Ricardi U, Filippi AR, Biasin E, Ciammella P, Botticella A, Franco P, et al. Late predict clinically relevant patient dose errors. Med Phys 2011;38:1037–44.
toxicity in children undergoing hematopoietic stem cell transplantation with [27] Zhen H, Nelms BE, Tomé WA. Moving from gamma passing rates to patient
TBI-containing conditioning regimens for hematological malignancies. DVH-based QA metrics in pretreatment dose QA. Med Phys 2011;38:5477–89.
Strahlenther Onkol 2009;185(2):17–20.

Please cite this article in press as: Tas B et al. Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility
and reliability. Radiother Oncol (2018), https://doi.org/10.1016/j.radonc.2018.08.005