ARTICLE IN PRESS

Medical Dosimetry ■■ (2017) ■■–■■

Medical Dosimetry
j o u r n a l h o m e p a g e : w w w. m e d d o s . o r g

Dosimetry Contribution:

Fine-tuning the normal tissue objective in eclipse for lung

stereotactic body radiation therapy
James P. Bell, M.S., R.T.T.,* Pretesh Patel, M.D.,† Kristin Higgins, M.D.,†
Mark W. McDonald, M.D.,‡ and Justin Roper, Ph.D., D.A.B.R.‡
*Department of Radiation Oncology, Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, TX;
†
Winship Cancer Institute of Emory University, 1356 Clifton Road NE, Building C, Atlanta, Georgia 30322; and ‡Hospital Corporation of America,
Sarah Cannon Cancer Center, Department of Radiation Oncology, 2410 Patterson Street, Basement Level, Nashville, TN 37203

A R T I C L E I N F O A B S T R A C T

Article history: The purpose of this study was to characterize the effects of the normal tissue objective (NTO)
Received 2 May 2017 on lung stereotactic body radiation therapy (SBRT) dose distributions. The NTO is a spatial-
Received in revised form 13 ly varying constraint used in Eclipse to limit dose to normal tissues by steepening the dose
November 2017
gradient. However, the multitude of potential NTO setting combinations challenges optimal
Accepted 13 November 2017
NTO tuning. In the present study, a broad range of NTO settings are investigated for lung
SBRT treatment planning with volumetric modulated arc therapy(VMAT). Ten prior lung SBRT
Keywords:
cases were replanned using NTO priorities of 1, 50, 100, 200, 500, and 999 in combination
NTO
with fall-off values of 0.01, 0.05, 0.10, 0.15, 0.20, 0.30, 0.50, 1.00, and 5.00 mm−1 and the au-
Fall-off
tomatic NTO. NTO distances to planning target volume (PTV), start dose, and end dose were
SBRT
1 mm, 100%, and 10%, respectively, for all 600 plans. Prescription dose covered 95% of the
PTV. The following metrics were recorded: conformity index (CI), ratio of the 50% prescrip-
tion isodose volume to PTV (R50%), maximum dose 2 cm away from PTV (D2cm), lung volume
of ≥20 Gy (V20Gy), maximum PTV dose (PTVmax), and monitor units (MUs). Differences between
prior plans and NTO plans were evaluated using the Wilcoxon signed-rank test. Different
combinations of NTO settings resulted in wide-ranging plan quality metrics: CI (1.00 to 1.54),
R50% (3.95 to 7.57), D2cm (33.4% to 67.9%), V20Gy (1.66% to 2.75%), MU (1.81 cGy−1 to 4.69 cGy−1),
and PTVmax (118% to 175%). Although no settings were optimal for all metrics, a fall-off of
0.15 mm−1 and a priority of 500 best satisfied institutional criteria. Compared with prior plans,
NTO plans resulted in significantly lower R50% (4.00 vs 4.35, p = 0.002), lower V20Gy (1.22% vs
1.32%, p = 0.006), and higher PTVmax (138% vs 122%, p = 0.002). All of the prior and well-
tuned NTO plans met Radiation Therapy Oncology Group (RTOG) 0813 guidelines. Lung SBRT
dose distributions were characterized across a range of NTO settings. NTO plans with well-
tuned settings compared favorably with prior plans.
© 2017 American Association of Medical Dosimetrists.

Introduction

Reprint requests to James P. Bell, M.S., R.T.T., Department of Radiation

Oncology, Simmons Comprehensive Cancer Center at the University of
For medically inoperable early-stage lung cancer pa-
Texas Southwestern Medical Center, Dallas, TX, USA. tients, stereotactic body radiation therapy (SBRT) has
E-mail: James.Bell@UTSouthwestern.edu emerged as a viable treatment option, providing an
https://doi.org/10.1016/j.meddos.2017.11.004
0958-3947/Copyright © 2017 American Association of Medical Dosimetrists
 ARTICLE IN PRESS
2 J.P. Bell et al. / Medical Dosimetry ■■ (2017) ■■–■■

ablative effect on tumors rivaling outcomes found with sur- 2) start dose (f0),
gical resection.1-3 In a recent review of retrospective studies, 3) end dose (f∞),
SBRT was recommended because of substantially better local 4) and fall-off (k).
control and overall survival rates compared with conven-
tional radiation therapy (RT) techniques.3 SBRT mandates high The NTO equationa is as follows:
accuracy and high precision RT; therefore, quality assur-
⎧ x ≥ xstart ⎫
ance standards are tighter than those associated with f ( x ) = ⎨ f0 − k( x − xstart ) + f∞ (1 − e − k( x − xstart ) ) , ⎬
conventionally fractionated RT.4-6 Successful implementa- ⎩ f0,< xstart ⎭
tion of SBRT requires accurate patient positioning, secure
The first parameter xstart is the distance away from a PTV
immobilization, and a distinctive set of planning strategies
border, which defines a plateau region of uniform dose abut-
for optimal delivery of highly biologically effective doses.3,7,8
ting a target volume.b The second parameter, f0, is the start
In contrast with the large treatment volumes and relative-
dose. The start dose may be set as a certain percentage of
ly uniform doses used in conventional RT, relatively small
the prescription dose and defines the dose level in the plateau
targets are treated in SBRT using highly conformal dose dis-
region. The third parameter, f∞, is the end dose. The end dose
tributions with sharp dose gradients. Excellent conformity
is the lowest dose penalized by the NTO. The location of the
and rapid dose gradients are important because healthy
end dose is influenced by the fall-off parameter k. This ex-
tissues that receive intermediate to high-dose spillage may
ponential decay constant may range from 0 to 10 (mm−1) and
become severely damaged, with the potential for long-
determines the steepness of the NTO curve beyond the dose
term toxicity.2
plateau. In addition to these shape parameters, the impor-
To achieve the desired dose distribution for SBRT of the
tance of the NTO is determined by a priority parameter.
lung, several treatment planning strategies may be em-
Priority may range from 0 to 1000 and determines the rel-
ployed clinically. Multiple static beams or arcs are often spread
ative importance of the NTO to any other optimization
over a wide angular range, including noncoplanar
constraints. The NTO has no effect when the priority is set
orientations.4,9 Additionally, treatment planners may adjust
to 0, whereas the highest allowable priority will apply a
beam weights, multileaf collimators, or other modifiers when
maximum penalty.
using 3-dimensional-conformal RT techniques. Inverse plan-
While the NTO has a flexible equation that allows for a
ning, e.g., intensity modulated radiation therapy (IMRT) and
customized dose profile penalty and weighting, there is little
volumetric modulated arc therapy (VMAT), is also used for
guidance as to which settings are optimal for a specific task.
SBRT. Inverse planning techniques may include optimiza-
Here, NTO settings were studied for the task of lung SBRT
tion structures such as concentric rings used to isotropically
treatment planning. A broad range of NTO priorities and fall-
steepen the dose distribution. Additional penalties may be
off values were investigated in an effort to determine settings
applied to preferentially spare sensitive healthy tissues.10 Al-
that achieve highly conformal dose distributions with sharp
though effective, the design and the use of ring structures
dose gradients. Plans were evaluated using dosimetric bench-
increase the planning time. The planner is faced with the
marks from Radiation Therapy Oncology Group (RTOG) 0813,
additional challenge of choosing the number of rings, the
a clinical trial on SBRT for early-stage lung cancer.11
ring width, gaps or overlaps, and the associated penalties.
For users of the Eclipse treatment planning system, the normal
tissue objective (NTO) is a tool available during optimiza- Methods and Materials
tion that requires no additional contouring time to achieve
sharp dose gradients beyond the target volume. Little time Ten consecutive patients who were previously treated at
or effort is needed to specify NTO settings; however, it is dif- our institution using SBRT for lung tumors were selected for
ficult to know which NTO settings are appropriate for a the present study. Cases were anonymized. Plans con-
particular plan. Guidelines on optimal NTO settings are lacking. sisted of 3 to 6 noncoplanar 6X-FFF VMAT arcs that broadly
Clarifying the NTO selection process during optimization could cover the collision-free zone. The collision-free zone was de-
potentially pave the way for NTO-based planning. termined before planning to make full use of dosimetrically
Eclipse has 2 types of NTO: an automatic formulism advantageous safe angles. The arc arrangement from the orig-
defined by the vendor and a spatially varying dose con- inal plan was used as a template when generating 60
straint defined by the user. The treatment planner sets the additional VMAT plans. Across the 60 plans for each of the
priority for both types. The shape of the user-defined NTO 10 cases, NTO priority values of 1, 50, 100, 200, 500, and 999
curve is described by 4 parameters:

a
J. A. Alakuijala and K.M. Pesola (Google Patents, 2008).
1) distance from planning target volume (PTV) border b
Varian Medical Systems, Inc. Eclipse Photon and Electron Algo-
(xstart), rithms Reference Guide. P1015026-001-A; 2015.
 ARTICLE IN PRESS
J.P. Bell et al. / Medical Dosimetry ■■ (2017) ■■–■■
were investigated for both the automatic and user-defined
NTOs. All user-defined NTO curves had an xstart of 1 mm, an
f0 of 100%, and an f∞ of 10%, whereas k varied from a gradual
fall-off of 0.01 mm−1 to a much steeper fall-off of 2.0 mm−1.
Plan optimization was simple and easy to implement. Only
the NTO and the PTV were penalized. Besides the NTO pri-
ority and fall-off settings described earlier, other NTO settings
were held constant. The PTV was penalized using a lower
objective with a priority of 100 set at the prescription dose
to cover 100% of the PTV. An upper PTV objective with a pri-
ority of 50 was set to limit the maximum dose to 140% of
the prescription. No constraints were placed on any of the
contoured organs at risk. All plans were optimized in auto-
matic mode with an intermediate dose calculation using the
Photon Optimization algorithm in Eclipse, version 13.6
(Varian Medical Systems Inc., Palo Alto, CA). No ring struc-
tures were used for optimization. Plans were neither paused
during optimization nor reoptimized following the final dose
calculation. The final calculation was performed using the
anisotropic analytical algorithm with tissue heterogeneity
corrections.
Before plan quality analysis, plans were normalized so that
the prescription dose covered 95% of a PTV while also en-
suring that 90% of the prescription dose covered at least 99%
of a PTV. Physicians gave consensus recommendations on
the rank order importance of plan quality metrics: first to
achieve adequate coverage of the PTV and then to mini-
mize high-dose spillage, low-dose spillage, and the lung
volume receiving ≥20 Gy (V20Gy). More specifically each plan
was evaluated based on the following criteria listed in
100
90
80
70
60
Dose [%]
50
40
30
20
10
0
0 0.5 1 1.5
Distance from PTV [cm]
Fig. 1. The NTO function defines the desired dose fall-off away from a PTV. In the present study, SBRT dose distributions are characterized as a func-
tion of NTO fall-off and priority. (Color version of figure is available online.)
3
descending order of importance: conformity index (CI), ratio
of the 50% prescription isodose volume to PTV (R 50% ),
maximum dose 2 cm away from a PTV (D2cm), V20Gy, and
maximum PTV dose (PTVmax). Monitor units (MUs) were also
recorded. Statistical significance with respect to differ-
ences between prior plans and NTO plans was evaluated
using the Wilcoxon signed-rank test.
Results
In the current study, a broad range of NTO settings were
investigated for 10 lung SBRT cases to characterize the effects
on plan quality metrics. PTVs ranged from 5.0 to 15.1 cc and
were relatively far from critical structures. Figure 1 shows
NTO curves from the investigated NTO fall-off values. The
dose profile from a representative original plan is also plotted
for reference. NTO priority values of 1, 50, 100, 200, 500, and
999 were studied for each of these curves.
NTO settings were shown to have a substantial effect on
the dose distribution and corresponding dose metrics. For
each metric, mean values were calculated across the 10 cases.
Figure 2 shows the mean CI, which ranged from 1.00 to 1.54.
CI approached 1.00 using an NTO priority value greater than
1 and a fall-off value of ≥0.1 mm−1. An automatic NTO with
priorities of 100 and 200 also resulted in a CI approaching
1.00.
Figure 3 shows a plot of mean R50% values. R50% ranged from
3.95 to 7.57. The automatic NTO performed poorly at reduc-
ing R50% to meet RTOG 0813 protocol guidelines.11 Only 1
automatic NTO did not result in a minor or major
NTO Fall-off
0.01
0.05
0.10
0.15
0.20
0.30
0.50
1.00
5.00
OP
2 2.5 3 3.5 4 4.5 5
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1.6

NTO Priority
1.5
1

Deviation
Minor Deviation
1.4 50
Conformity Index

100

Minor
1.3
200
1.2
500

Deviation
No Deviation
1.1 999

No
1

0.01 0.1 1 Automatic NTO

NTO Fall-off

Fig. 2. Conformity index. Each data point is the mean value from 10 cases (RTOG 0813 deviation thresholds are marked with dashed lines.). (Color
version of figure is available online.)

deviation, and it was outperformed by all user-defined NTOs
of the same priority with fall-off values of ≥0.1 mm−1.
Mean D2cm values can be seen in Fig. 4. D2cm ranged from
33.4% to 67.9%. Lowest values of D2cm were obtained with a
fall-off set to 0.15 mm−1 and a priority of 500. As with R50%,
the automatic NTO typically performed more poorly than the
user-defined NTO.
A plot of mean MU values is shown in Fig. 5. MUs per cGy
ranged from 1.81 to 4.69 cGy−1. The total number of MUs from
all fields was divided by the nominal daily dose. A higher
NTO priority typically reduced the number of MUs.
Mean lung V20Gy values ranged from 1.66% to 2.75%. Results
are plotted in Fig. 6. In general, lung V20Gy decreased as NTO
priority increased, although the decrements were relative-
ly small. In all cases, lung V20Gy was well below RTOG 0813
minor and major deviation limits of 10% and 15%.
A plot of mean PTVmax dose values is shown in Fig. 7. The
PTVmax dose ranged from 118% to 175%. In general, the au-
tomatic NTO performed worse than the user-defined NTO
as demonstrated in Figs. 2 to 6 and yielded lower PTVmax
values as seen in Fig. 7. As NTO priority and fall-off values
increased, so did PTVmax. For two of the NTO setting com-
binations, the recommended upper limit of 167% was
exceeded.
Although no combination of NTO settings were optimal
for all of the dose metrics, an NTO with a fall-off value of
0.15 mm−1 and a priority of 500 best satisfied the rank order
criteria. Median results from cases with well-tuned NTO set-
tings (priority of 500, fall-off of 0.15 mm −1 ) were then
compared with the median results from prior plans of the
same 10 cases. Statistical significance was assessed with the
Wilcoxon signed-rank test. Comparisons of the median

7.5 NTO Priority

Deviation
Deviation
Major

1
Major

6.5 50

100
6
R50

Deviation
Deviation

200
Minor
Minor

5.5

500
5
999
Deviation

4.5
No

3.5
0.01 0.1 1 Automatic NTO
NTO Fall-off

Fig. 3. R50. Each data point is the mean value from 10 cases (RTOG 0813 thresholds are marked with dashed lines.). (Color version of figure is avail-
able online.)
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J.P. Bell et al. / Medical Dosimetry ■■ (2017) ■■–■■ 5

70

Deviation
Deviation
Major
Major
65 NTO Priority
1
60
50

Deviation
Minor
55
100
D2cm [%]

50
200

45
500

Deviation
No
40 999

35

30
0.01 0.1 1 Automatic NTO
NTO Fall-off

Fig. 4. D2cm. Each data point is the mean value from 10 cases. (RTOG 0813 thresholds are marked with dashed lines). (Color version of figure is
available online.)

results from the 10 well-tuned NTO and prior cases were as
follows: CI of 1.02 vs 1.03 (p = 0.133), R50% of 4.00 vs 4.35
(p = 0.002), D2cm of 34.5% vs 36.5% (p = 0.131), V20Gy of 1.22%
vs 1.32% (p = 0.006), MUs of 2.76 cGy −1 vs 2.88 cGy −1
(p = 0.131), PTVmax of 138% vs 122% (p = 0.002), spinal cord
max of 3.78 Gy vs 3.57 Gy (p = 0.322), and heart max of
5.22 Gy vs 6.64 Gy (p = 0.313). In all cases, both the well-
tuned NTO and prior plans comfortably satisfied RTOG 0813
guidelines.11
Figure 8 depicts the isodose distributions from plans gen-
erated with varying fall-off values, all with an NTO priority
of 500. Note that plans with more isotropic isodose distri-
butions have relatively lower levels of low-dose spillage, as
shown by the curve height outside the PTV. A profile of the
PTV is drawn at the prescription dose level for reference.
Discussion
In the present study, the dosimetric effects of NTO set-
tings were characterized for lung SBRT. VMAT optimization
in Eclipse was simplified, consisting of the NTO and lower
and upper constraints on a PTV. No rings or other struc-
tures were penalized in the optimization. Following
institutional criteria for plan evaluation, a well-tuned NTO
had a fall-off of 0.15 mm−1 and a priority of 500. This com-
bination of NTO settings achieved high conformity,
minimized low-dose spillage, and required relatively few
MUs. When compared with median results from the 10 prior
cases, well-tuned settings of the NTO outperformed prior
cases with respect to achieving lower R50% and lung V20Gy. The
results (R50% of 4.00 vs 4.35, p = 0.002, lung V20Gy of 1.22% vs

4.5 NTO Priority

1
4
50
Monitor Units/cGy

3.5 100

200
3
500
2.5
999

1.5
0.01 0.1 1 Automatic NTO
NTO Fall-off

Fig. 5. Monitor units. Each data point is the mean value from 10 cases (lower monitor units = less complex MLC shaping). (Color version of figure is
available online.)
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16

14 NTO Priority
1
12
50
Lung V20Gy [%]

10
100
8
200

6
500

4 999

0
0.01 0.1 1 Automatic NTO
NTO Fall-off

Fig. 6. V20Gy. Each data point is the mean value from 10 cases (RTOG 0813 thresholds are marked with dashed lines.). (Color version of figure is
available online.)

1.32%, p = 0.006) were statistically significant. Although it is
possible that prior plans could be improved by using dif-
ferent rings or penalties, NTO plans had the advantage of
easier implementation as compared with ring-based plan-
ning; the 4 NTO parameters were defined within seconds.
All plans were well within RTOG 0813 guidelines.
Low-dose spillage is an important concern with SBRT. R50%
is a common metric for quantifying low-dose spillage in lung
SBRT.12 The R50% primarily describes intermediate dose spill-
age that is absorbed by healthy tissue beyond the target
border. Patients undergoing SBRT of the lung may have pre-
existing pulmonary limitations; therefore, relatively small
changes in R50% could cause significant negative effects with
respect to pulmonary function.12 Acceptable values of the
R50% are determined by the PTV volume and have been
defined in table 1 of RTOG 0813.11 Plans generated with
well-tuned NTO settings in this study achieved R50% values
within the RTOG 0813 protocol that were significantly lower
than R50% values from the prior cases utilizing the same
noncoplanar arc beam orientations. Similar trends were found
when comparing D2cm values, another metric of low-dose
spillage, although results were not statistically significant.
The mean PTVmax was higher for NTO plans compared with
prior plans: 138% vs 122%, p = 0.002. The upper objective
penalty for the target was set at 50, whereas the objective
itself was 140% of the prescription dose for each of the cal-
culated NTO plans in the present study. Typically, planning
strategies that obtain sharper dose gradients often result in
a higher maximum dose inside of a PTV. A higher PTV dose
may be perceived as beneficial as the highest dose in the
center of the field could coincide with a hypoxic and there-
fore more radioresistant tumor core.13,14 All prior plans

180

170 NTO Priority

1
-60%
90% -60%

160
50
PTV Max Dose [%]

surface: 90%

150 100
isodose surface:

200
140
Prescription isodose

500
130
Prescription

999

120

110
0.01 0.1 1 Automatic NTO
NTO Fall-off

Fig. 7. PTVmax (RTOG 0813 expected range is within dashed lines.). (Color version of figure is available online.)
 ARTICLE IN PRESS
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A B
Fig. 8. (A) Dose line profiles of plans with priority set to 500 and fall-off values of 0.01 (red), 0.1 (yellow), 0.15 (green), 0.5 (cyan), 1.0 (purple), and
5.0 (magenta). (B) Axial view of isodose line distributions of plans with priority of 500 and a fall-off, from top left: 0.01, 0.1, 0.15, 0.5, 1.0, and 5.0.
(Color version of figure is available online.)
achieved a PTVmax well below the RTOG 0813 upper limit,
although perhaps with the trade-off of relatively worse low-
dose spillage.11 In contrast, certain NTO plans exceed the
upper limit, although most were within the acceptable vari-
ation range.11,14
Results show an interplay effect between PTV dose and
low-dose spillage. By tuning NTO settings and allowing a
maximum PTV dose of approximately 140%, low-dose
spillage—D2cm in particular—was minimized. As shown in
Fig. 8, a plan with these settings had relatively symmetric
isodose lines forming shells around the PTV. Whereas sym-
metric dose distributions appear to correspond to reduced
low-dose spillage and may be desirable in many cases, asym-
metric dose distributions might be beneficial for sparing a
nearby critical structure. In such cases, the NTO alone may
not be adequate for meeting normal tissue constraints.
The cases evaluated in the present study had relatively
small PTVs, which were relatively far from any critical struc-
tures. Tumor size is related to SBRT treatment outcomes.15
A recent study comparing T1 and T2 lung tumors found that
larger tumors were associated with higher local recur-
rence and reduced survival rates.15 Additionally, tumor
location influences SBRT planning techniques and the dose
to healthy tissues. RTOG 0813 proposes that dose-volume
limits be used for tissues located in close proximity to the
PTV.11 Although NTO tuning could be a useful strategy for
dose escalation or greater sparing of normal tissues,
7
additional research is needed to determine optimal NTO set-
tings across the range of tumor sizes and tumor locations
seen clinically.
The NTO has been commercially available for some time;
however, the authors do not know of any previously pub-
lished work on optimal NTO settings for lung SBRT. A
previous study has investigated SBRT planning with the use
of ring structures.14 The current study investigates a broad
range but not an exhaustive set of NTO parameters. The
current study explores how the calculated dose distribu-
tion is affected by NTO priority and fall-off, parameters that
respectively describe the steepness of the dose gradient and
the importance of achieving that gradient in relation to other
optimization constraints, i.e., PTV coverage. The param-
eters were investigated, given their conceptual relationships,
along with goals of achieving steep dose gradients beyond
a PTV and adequately covering a PTV with the prescribed
dose. A broad array of priority and fall-off combinations were
studied; however, other NTO parameters were held con-
stant. The parameters xstart and f∞ were set at 100% and 10%
of the prescription dose, whereas xstart was 1 mm. The mo-
tivation for these choices was to deliver full dose to a PTV
while penalizing much of the low-dose wash. Limiting the
extent of any high-dose spillage to a small rind around a PTV
was an additional concern. Although beyond the scope of
the present study, these NTO parameters could be tuned in
combination with the fall-off and priority. Furthermore, other
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8 J.P. Bell et al. / Medical Dosimetry ■■ (2017) ■■–■■
plan evaluation criteria could be considered, e.g., the unified
dosimetry index, which integrates the CI, the coverage index,
the homogeneity index, and the dose gradient index all into
1 score.16-18 Optimal NTO settings may also depend on the
beam arrangement. The NTO is limited to 1 dimension,
whereas the 3-dimensional dose distribution depends
strongly on the beam arrangement. Further investigation is
needed to determine optimal NTO settings across the many
possible treatment planning applications.
Conclusions
Lung SBRT dose metrics were characterized across a
broad array of NTO priority and fall-off settings. The range
of dosimetric results, some unacceptable and many less
than optimal, demonstrates the importance of selecting
appropriate NTO settings and the exponential effects of
the fall-off parameter (k). An automatic NTO is not recom-
mended for lung SBRT planning because of poor performance
at reducing low-dose spillage. Plans with well-tuned NTO
settings (priority of 500, fall-off of 0.15 mm−1) compared
favorably with prior plans created with ring structures,
achieving significantly lower R50% and lung V20 values.
Based on the ease of NTO planning and the corresponding
results found in the present study, when well-tuned, the
NTO is a viable and powerful treatment planning tech-
nique for lung SBRT.
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