Received: 24 March 2017 | Revised: 18 May 2017 | Accepted: 23 May 2017

DOI: 10.1002/acm2.12127

RADIATION ONCOLOGY PHYSICS

Feasibility of CBCT-based dose with a patient-specific

stepwise HU-to-density curve to determine time of
replanning

Shifeng Chen1 | Quynh Le2 | Yildirim Mutaf3 | Wei Lu1 | Elizabeth M. Nichols1 |
Byong Yong Yi1 | Tish Leven2 | Karl L. Prado1 | Warren D. D’Souza1

1
Department of Radiation Oncology,
University of Maryland School of Medicine, Abstract
Baltimore, MD, USA Purpose: (a) To investigate the accuracy of cone-beam computed tomography
2
Department of Radiation Oncology,
(CBCT)–derived dose distributions relative to fanbeam–based simulation CT-derived
University of Maryland Medical Center,
Baltimore, MD, USA dose distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the
3
Department of Radiation Oncology, appropriateness of replanning.
Boston University School of Medicine,
Boston, MA, USA Methods and materials: Image data corresponding to 40 patients (10 head and neck
[HN], 10 lung, 10 pancreas, 10 pelvis) who underwent radiation therapy were ran-
Author to whom correspondence should be
addressed. Shifeng Chen domly selected. Each patient had both intensity-modulated radiation therapy and
E-mail: schen@umm.edu; Telephone: 410- volumetric-modulated arc therapy plans; these 80 plans were subsequently recom-
328-3544
puted on the CBCT images using a patient-specific stepwise curve (Hounsfield
units-to-density). Planning target volumes (PTVs; D98%, D95%, D2%), mean dose,
and V95% were compared between simulation-CT–derived treatment plans and
CBCT-based plans. Gamma analyses were performed using criterion of 3%/3 mm
for three dose zones (>90%, 70%~90%, and 30%~70% of maximum dose). CBCT-
derived doses were then used to evaluate the appropriateness of replanning deci-
sions in 12 additional HN patients whose plans were previously revised during radi-
ation therapy because of anatomic changes; replanning in these cases was guided
by the conventional observed source-to-skin-distance change-derived approach.
Results: For all disease sites, the difference in PTV mean dose was 0.1%  1.1%, D2%
was 0.7%  0.1%, D95% was 0.2%  1.1%, D98% was 0.2%  1.0%, and V95% was
0.3%  0.8%; For 3D dose comparison, 99.0%  1.9%, 97.6%  4.4%, and 95.3% 
6.0% of points passed the 3%/3 mm criterion of gamma analysis in high-, medium-, and
low-dose zones, respectively. The CBCT images achieved comparable dose distribu-
tions. In the 12 previously replanned 12 HN patients, CBCT-based dose predicted well
changes in PTV D2% (Pearson linear correlation coefficient = 0.93; P < 0.001). If 3% of
change is used as the replanning criteria, 7/12 patients could avoid replanning.
Conclusions: CBCT-based dose calculations produced accuracy comparable to that
of simulation CT. CBCT-based dosimetry can guide the decision to replan during the
course of treatment.

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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2017 University of Maryland School of Medicine. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American
Association of Physicists in Medicine.

J Appl Clin Med Phys 2017; xx: 1–6 wileyonlinelibrary.com/journal/jacmp | 1

2 | CHEN ET AL.

PACS
87.55.D

KEY WORDS
adaptive radiation therapy, CBCT-based dose calculation, HU-to-density curve

1 | INTRODUCTION dose calculation using a patient-specific stepwise HU-to-density

curve (i.e., patient CBCT HUs were converted to only six classes
The need for adaptive radiotherapy has been demonstrated by many of materials: air, lung, adipose, tissue, cartilage/bone, and other
investigators.1–3 New plans are adapted throughout the weeks-long high-density material). The method is similar to density override in
course of fractionated radiotherapy to account for patient geometry its assignment of six classes of materials. Most modern treatment
changes resulting from weight loss, organ deformation, tumor shrink- planning systems provide a density override function, so that this
age, and other causes. New adaptive plans may also be needed if method could be used widely in clinical practice. The purpose of this
the immobilization device needs to be adjusted or remade for variety study was to (a) investigate the accuracy of CBCT-based dose calcu-
of reasons. For some patients receiving intensity-modulated radio- lations in the RayStation treatment planning system, and (b) study
therapy (IMRT) or volumetric-modulated arc therapy (VMAT), the the feasibility of using CBCT-based dose to select the appropriate
significant benefit of replanning has been demonstrated.4 The fre- treatment replanning time. In this study, dose calculation accuracy
quency of replanning in patients with head and neck cancer was was assessed using 80 IMRT/VMAT plans for four anatomic sites:
reported to be 32%–70%, depending on criteria.5 It is challenging, head and neck (HN), lung, pancreas, and prostate. The appropriate-
however, to decide on the appropriate time for replanning. Several ness of replanning decisions was evaluated with data from 12 res-
investigators have looked for indicators to predict substantial dosi- canned patients with head and neck cancer.
metric change. Although correlations between several parameters
(such as weight loss, skin separation, and others) and dose change to
2 | METHODS AND MATERIALS
target or organ at risk (OAR) were observed,4–6 no single parameter
can be reliably used to decide the time of replanning for patients
2.A | Patient data
with head and neck cancer.4 Therefore, decisions on replanning are
frequently based on the practical experience of clinicians. Image data from 40 patients who underwent radiation therapy at
The main challenge in initiating the replanning process is a lack of our institution were randomly selected for this institutional review
tools for estimation of dosimetric changes for targets and OARs. board approved retrospective study; patients with large geometry
Onboard kV cone-beam CT (CBCT) is now widely available, and change (external body contour change >1 cm between planning CT
CBCT-based dose calculation makes it possible to evaluate dosimetric and CBCT) were excluded. All patients received step-and-shoot
change during the course of treatment. Although kV CBCT technol- IMRT or VMAT treatments in our clinic for four anatomic sites: HN,
ogy is mainly used to set up patients and localize anatomy, its poten- lung, pancreas, and prostate. If the patient received IMRT (or VMAT)
tial for use in dose calculation has been recognized and reported.7–10 treatment, a complementary VMAT (or IMRT) plan was retrospec-
Dose calculation accuracy using CBCT images has been evaluated by tively made, with dose distributions comparable to the original clini-
investigators.8,9,11–13 The main source of dosimetric error stemming cal plan. In this way, a total of 80 plans were included in this study.
from CBCT-based dose calculations (relative to fan-beam-based CT All patients were treated on Varian linacs (iX, Trilogy, or TrueBeam;
simulation) comes from the uncertainty in Hounsfield unit (HU)-to- Varian Medical Systems, Palo Alto, CA, USA). Each linac was integrated
electron density conversion of CBCT images. As a more direct with an onboard kV CBCT (OBI; Varian). All patients underwent CBCT
approach, phantom-based calibration of the HU-to-electron density scans prior to their first treatment. CBCTs of the first treatment day
curve was investigated.7–9,13 Unlike fan-beam CT, kV CBCT suffers were used for subsequent dose calculation to minimize potential
from scatter, which results in greater HU uncertainty.13–16 Because anatomical variations between CT simulation and the start of the radi-
CBCT HUs vary with disease site, scanning mode, scanning range, ation treatment regimen. The time interval between CT simulation and
and other factors,13 multiple calibration curves may be required. the CBCT is 13.3  4.3 days. Patient selection intentionally mimicked
Moreover, HUs are dependent on patient size,17,18 making this the real clinical world, so that CBCT images with artifacts or relatively
method even more challenging. An alternative method that relies on low image quality were still included in the study.
mapping of electron density values from planning CT to CBCT images
was introduced.8,19–21 Because of the complexity of these methods,
2.B | Patient-specific stepwise HU-to-density curve
CBCT-based dose is not commonly used in routine clinical practice.
A recently developed treatment planning system RayStation V5.0 Unlike the CT-based planning that uses only a single CT-to-electron
(RaySearch Laboratories; Stockholm, Sweden) provides CBCT-based density calibration curve in the treatment planning system, a
CHEN ET AL. | 3

patient-specific stepwise HU-to-density curve was created for each

2.D | Comparison between CT and CBCT-based
patient, assigning each voxel of CBCT images to one of the following
replanned dosimetry
categories of material (mass density): air (0.00121 g/cm3), lung (0.26 g/
cm3), adipose (0.95 g/cm3), tissue (1.05 g/cm3), cartilage/bone Retrospective data from 12 additional patients with head and neck
(1.6 g/cm3), and other (3 g/cm3). The treatment planning system is cancer were selected for evaluation of the method. These 12
RayStation V5.0 (RaySearch Laboratories; Stockholm, Sweden), which patients were not included in the original cohort of 40 patients
provides the tool to adjust the HU threshold for each material via described above. Because of weight loss and source-to-skin dose
best match with the known material type (Fig. 1). The HU threshold changes, these patients had been rescanned based on clinicians’
was adjusted for each patient. The optimal thresholds were attained judgments and evaluated based on the new CT results. CBCT images
by identifying the range of HUs for each material category based on acquired within 3 days of the rescanned CT images were available
the CBCT. The corresponding mass densities were used in dose for these patients. The original IMRT/VMAT plans were calculated
calculation. based on the rescanned CT and CBCT images. As a result of weight
loss, the largest change among the investigated variables was PTV
D2% (near-maximum dose). The other variables listed above had
2.C | CBCT-based dose calculation accuracy
small but better changes, i.e., the PTV coverage was better, so only
For each patient, CBCT scans were transferred to the RayStation changes in PTV D2% between original plans and rescanned CT/
treatment planning system and then registered to the planning CT CBCT images were compared. The Pearson linear correlation coeffi-
based on the bony anatomy. Contours, such as planning target vol- cient was calculated.
ume (PTV) and OARs, were copied from the planning CT to the
CBCT image via rigid registration. The dose was recalculated using
3 | RESULTS
the original dose calculation algorithm, but using the CBCT image
for both IMRT and VMAT plans. The dose calculated based on
3.A | CBCT-based dose calculation accuracy
CBCT was compared to that based on planning CT (Fig. 2). Differ-
ences between the two plans were documented for the following Dose differences between planning CT-based plans and CBCT-based
dose–volume variables: dose received by 98% of the PTV (D98%, plans for PTV are summarized in Table 1. Gamma analysis results are
near-minimum dose), PTV D95%, PTV D2% (near-maximum dose), shown in Table 2. CBCT-based dose calculation accuracy does not
PTV mean dose, and PTV volume receiving ≥95% of prescription correlate with the planning technique (VMAT vs IMRT). No differ-
dose (V95%). Gamma analysis was performed using a criterion of ence was observed between VMAT and IMRT plans for any disease
3%/3 mm for three dose zones: the zone receiving ≥90% of maxi- sites. Results for all disease sites are summarized in Tables 1 and 2.
mum dose (high-dose region), the zone receiving 70%–90% of maxi-
mum dose (medium-dose region), and the zone receiving 20%–70%
3.B | Feasibility for evaluating dosimetry
of maximum dose (low-dose region). These three zones represented
three types of regions of interest: PTV, OARs adjacent to PTV, and The International Commission on Radiation Units & Measurements
OARs/normal tissue at some distance from the PTV and receiving (ICRU) Report 8322 recommends that 85% of target points should
low dose. meet the criteria of absorbed dose difference within 5% if points are

F I G . 1 . Example showing mass density on CBCT images (left) and HU thresholds to define material type (right). Mass density was assigned
to each voxel via mapping CBCT HUs to six classes of materials (patient-specific HU-to-density table; right). HU threshold to define different
materials can be adjusted via best match with known tissue on CBCT. Black = air; pink = adipose; light blue = tissue; gold = cartilage/bone
(lung and other material not shown).
4 | CHEN ET AL.

F I G . 2 . Planning CT (top) and CBCT

(bottom) for a patient with head and neck
cancer. Blue lines indicate PTV, and the
color wash indicates the percentage of the
prescription dose.

T A B L E 1 PTV dose–volume difference between CBCT-based and CT-based plans.

Head and neck Lung Pancreas Pelvis All patients
Disease site (mean  SD) (mean  SD) (mean  SD) (mean  SD) (mean  SD)
Mean dose difference 0%  0.6% 0.4%  1.1% 0.2%  1.0% 0.2%  1.3% 0.1%  1.1%
D2% difference 0.5%  0.6% 0.9%  1.2% 1.1%  1.1% 0.4%  1.3% 0.7%  1.1%
D95% difference 0.4%  0.7% 0.2%  1.4% 0.0%  0.9% 0.4%  1.2% 0.2%  1.1%
D98% difference 0.6%  0.8% 0.2%  1.2% 0.0%  0.9% 0.4%  1.1% 0.2%  1.0%
V95% difference 0.4%  0.4% 0.1%  0.7% 0.0%  0.5% 0.6%  0.9% 0.3%  0.8%

T A B L E 2 Gamma analysis results (passing rate using 3%/3 mm criterion) comparing CBCT-based plan dose and CT-based planning dose.
Disease site Head and neck (mean  SD) Lung (mean  SD) Pancreas (mean  SD) Pelvis (mean  SD) All patients (mean  SD)
High-dose zones 98.3%  1.5% 96.1%  5.0% 99.1%  2.4% 100%  0% 99.0%  1.9%
Medium-dose zones 92.9%  5.5% 98.7%  3.4% 100%  0% 98.9%  2.5% 97.6%  4.4%
Low-dose zones 92.1%  7.2% 98.7%  2.2% 96.9%  4.9% 95.8%  5.7% 95.3%  6.0%

located at low-gradient areas (dose change <20%/cm) or that

3.C | Comparison between CT and CBCT-based
distance-to-agreement should be within 5 mm if points are located
replanned dosimetry
at high-gradient areas (dose change >20%/cm). CBCT-based dose
accuracy was determined to be above the ICRU recommendation; Changes in near-maximum dose of PTV (D2%) between initial plan-
therefore, the PTV dose–volume parameters (mean dose, D2%, ning CT and rescanned CT/CBCT were calculated for 12 patients
D95%, D98%, and V95%) were used to decide the replanning time. with HN cancer. Changes based on CBCT and those based on res-
Gamma analysis using the criterion of 3%/3 mm can serve the same canned CT are plotted in Fig. 3 and are significantly correlated (Pear-
purpose. son linear correlation coefficient = 0.93; P < 0.001). The change in
CHEN ET AL. | 5

D2% based on CBCT predicts the change based on rescanned CT, 0.5%  0.6%, 0.4%  0.7%, and 0.4%  0.4% for HN patients.
which was assumed to be ground truth. If 3% of the change in D2%, Because most of treatment planning systems provide the function of
for example, was used as the replanning criterion, seven of the 12 density overriding, our method can be easily implemented in clinical
patients could have avoided replanning procedures. Note that 3% of practice. The CBCT dose was compared to the dose in the initial
the change is an arbitrarily chosen criterion. The replanning criteria plan, which was assumed to be ground truth. Both delivery modali-
should depend on the clinical need, and it is beyond the scope of ties (VMAT and IMRT) were compared, and we conclude that the
this paper. accuracy of CBCT-based dose calculation is not dependent on deliv-
ery technique. Four treatment sites (head and neck, lung, pancreas,
and pelvis) were included in this study, and the accuracy of CBCT-
4 | DISCUSSION
based dose calculation was slightly related to the treatment sites.
Both dose statistics and gamma analysis showed that an accuracy of
4.A | CBCT-based dose calculation accuracy
3% is achievable for CBCT-based dose calculations. The gamma anal-
Although many researchers7–13 have investigated CBCT-based dose ysis was performed for three dose zones representing PTV, OARs
calculations and their use in replanning or online adaptive planning, receiving high dose, and OARs receiving low dose.
clinical implementation has remained challenging because of the
complexity of the technique or inability to achieve the accuracy
4.B | Feasibility to determine the best replanning
required by treatment planning. In this study, we assessed the accu-
time
racy of the CBCT-based dose calculations using patient-specific step-
wise HU-to-density curves and investigated the feasibility of using The recently published ICRU Report 83 suggests defining dose accu-
this method to determine replanning time. Six types of materials racy with dose–volume statistics rather than the point dose, as rec-
were used to convert the HU to density. A similar method (manually ommended by ICRU Report 50 and 62; therefore, PTV dose–volume
“overriding” density of all structures of interest on CBCT images) statistics (D2%, D95%, D98%, V95%) and gamma analysis were used
was investigated by Fotina et al.,12 who documented this as an to assess CBCT-based dose accuracy in this study. Our results
attractive approach. Both their and our studies included pelvis showed that CBCT-based dose accuracy was much better than
patients and HN patients treated with IMRT. For their study, the absorbed dose accuracy as suggested by ICRU Report 83; therefore,
dose or coverage differences (D2%, D98%, and V95%) between all of these parameters in this study are feasible for indication of the
planning CT and CBCT were 3.2%  3.4%, 0.6%  1.8%, and dose difference between initial planning dose and CBCT-based dose.
0.9%  2.9% for pelvis patients, and 2.3%  7.5%, 0.9%  7.1%, CBCT-based dose can quantitatively provide the dosimetry change
and 1.9%  1.4% for HN patients. Our method shows a slightly (at a 3% accuracy level) to the physician. Data from the 12 patients
better dose accuracy: the dose or coverage differences (D2%, D98%, with HN cancer assessed for validation purposes showed that the
and V95%) between planning CT and CBCT were 0.4%  1.3%, change of PTV D2% was significantly correlated between CBCT data
0.4%  1.1%, and 0.6%  0.9% for pelvis patients, and and rescanned CT data. With the 3% criterion, seven of these 12
patients could have avoided rescanning procedures, despite changes
in weight and large changes in skin-to-source doses after initial plan-
ning. Changes in these parameters during treatment are feasible to
help physicians decide whether a patient needs rescanning. Replan-
ning criteria should be determined based on clinical need and ratio-
nale. Further investigation of guidelines for these criteria in specific
clinical situations is needed before this method can be applied in the
clinical setting. Specific OAR doses may be used to determine the
time of replanning, depending on the case. Because CBCT is becom-
ing a routine tool in imaging-guided radiotherapy, the CBCT-based
dose calculation can be thought of as an extra benefit for patients,
conveying the potential to avoid unnecessary rescanning, with
resulting benefits in lower cumulative radiation dose, less treatment
delay, and reduced medical costs.

4.C | Limitation of the study

Although 40 patients were selected to minimize geometric differ-
F I G . 3 . Change in PTV D2% relative to the prescription dose ences between planning CT and CBCT, small differences may still
based on CBCT vs change based on CT2 for 12 patients with head exist. The dosimetry difference between the CBCT plan and planning
and neck cancer who were rescanned because of weight loss.
CT mainly results from the patient-specific stepwise HU-to-density
6 | CHEN ET AL.

curve, but geometric change, leading to dosimetric differences, can- 6. Lee C, Langen KM, Lu W, et al. Assessment of parotid gland dose
not be excluded. However, without geometric change, dosimetric changes during head and neck cancer radiotherapy using daily mega-
voltage computed tomography and deformable image registration.
agreement between the two dose calculations would be expected to
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CONFLICT OF INTEREST
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The authors declare no conflict of interest.
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