A Retrospective Evaluation of Mixed Energy Volumetric Modulated Arc Therapy for Anal

Cancers with Lymph Node Involvement

Mikayla Eskens, BS; Helen Nguyen, BS; Will Deere, BS, RT(T); Matt Tobler, CMD; Ashley
Hunzeker, MS, CMD; Nishele Lenards PhD, CMD, RT(R)(T), FAAMD; Alyssa Olson, MS,
RT(T), CMD
Medical Dosimetry Program at the University of Wisconsin, La Crosse, WI

ABSTRACT
Applying dual, or mixed photon energies during radiation therapy is a common practice in three-
dimensional conformal radiation therapy (3D-CRT), used to provide uniform dose coverage to a
planning target volume (PTV) that ranges in depth from the skin surface. Though this application
was once the convention for treating anal cancers with lymph node involvement (AC-LNI), the
advantages of volumetric modulated arc therapy (VMAT) have proven VMAT to be the optimal
form of therapy for AC-LNI. Recent literature has uncovered benefits in employing multiple
photon energies in VMAT planning for specific pelvic cancers. A retrospective study was
completed to assess the impact of implementing mixed energy VMAT planning in comparison to
conventional single energy VMAT planning for AC-LNI. Data from 20 patients with AC-LNI
was collected in order to analyze the dosimetric effects of mixed energy VMAT treatments in
terms of PTV coverage, monitor unit (MU) usage, and organs at risk (OAR) sparing. For each
patient three treatment plans were created: a single energy 6 MV plan, a single energy 10 MV
plan, and one mixed 6 MV and 10 MV energy plan. Analysis of the resulting dosimetric
outcomes showed that the single energy VMAT plans were better able to spare dose to OAR,
however the mixed energy plans provided better PTV coverage. This study concludes that mixed
energy VMAT plans may provide some benefit to treating AC-LNI.

Key Words: Radiation Therapy, VMAT, Optimization, AC-LNI, Mixed Energy

Introduction
While creating a radiation therapy treatment plan, medical dosimetrists are able to utilize
photons of varying energies depending on the depth of the planning target volume (PTV).
Tumors that are more superficial require low energy photons. Deep-seeded tumors require higher
energy photons because of their ability to penetrate through matter. This is also the case when
skin irradiation is desirable. A study comparing photon energies in prostate volumetric
modulated arc therapy (VMAT) treatments demonstrated lower relative integral dose, monitor
units, depth of maximum dose (dmax), and bladder volume receiving 30 Gy (V30) for the 10 MV
plans versus the 6 MV plans.1 Though higher energies can be beneficial in reaching deep seated
tumors, photon energies higher than 10 MV are not recommended for VMAT treatments due to
the additional dose contributed from photo-neutron contamination.2 Additionally, 6 MV and 10
MV VMAT treatments were found to be more beneficial than using 15 MV photons in a study
by Yadav et al.3 Some cancers, such as those found in the pelvis region, range drastically in
depth from the skin surface; these can be difficult to treat and may necessitate the use of multiple
photon energies. One such treatment, historically treated using multiple photon energies, is anal
cancers with lymph node involvement (AC-LNI).
Multiple treatment plan methods have been implemented in treating AC-LNI in attempt
to produce adequate PTV coverage while preventing organs at risk (OAR) from receiving excess
dose. Before VMAT and dynamic intensity modulated radiation therapy (IMRT) technology was
available, AC-LNI was conventionally treated with mixed energy three-dimensional conformal
radiation therapy (3D-CRT). These mixed energy 3D-CRT treatment plans consisted of deep-
penetrating static beams (15 MV or 18 MV photons) and superficially penetrating static beams (6
MV photons or various energies of electrons) in order to treat both the deep seated anal tumor
and superficial nodes respectively.4,5 With the introduction of VMAT and IMRT, 3D-CRT
became unsuitable for treating AC-LNI. Multiple studies, including those by Vieillot et al,6
Clivio et al,7 and Franco et al8 support the current convention of VMAT as the optimal form of
treatment for AC-LNI. Research in combining traditional methods, such as mixed energy
treatments, with the more advantageous VMAT therapy for pelvic cancers other than AC-LNI
has shown interesting results in recent years.
Investigation into using mixed energy VMAT planning for prostate cancer has shown
benefits in terms of dose conformity and sparing dose to OAR. In one study, Park et al9
evaluated mixed energy treatments for prostate patients undergoing IMRT, and concluded that
using mixed energies for IMRT prostate plans can enhance the overall quality of the plan by
reducing dose delivered to organs at risk (OAR). Another study by Momin et al10 showed that
mixed-energy VMAT plans could be used to improve dose conformity to the PTV, and further
limit dose delivered to OAR. Shyam Pokharel11 also studied the dosimetric impact of mixed‐
energy VMAT plans, and concluded that mixed-energy VMAT could reduce integral dose and
minimize the dose to the rectum in bladder when used for high-risk prostate cancer cases. Lastly,
Mcgeachy et al12 used an external optimizer to provide beam energy as a degree of freedom in
IMRT optimization processes and found that plans could be dosimetrically improved through
sparing dose delivered to OAR.
A mixed energy VMAT treatment may present dosimetric advantages for treating AC-
LNI. Using different photon energies during radiotherapy is a method medical dosimetrists
implement in order to treat target volumes at various depths. The large range in treatment depth
from the skin in AC-LNI has historically been treated using mixed energy 3D-CRT. Treating
AC-LNI using mixed energy 3D-CRT is no longer clinically conventional because VMAT has
been established as the optimal form of treatment. Research in combining 3D-CRT mixed energy
methods with VMAT treatment has shown some benefits for simple pelvic cancers, but has not
been investigated for cancers with a large range in treatment depth, such as AC-LNI. Through
the results of the above studies, a need was presented for further research into the viability of
mixed energy VMAT planning for applicable pelvic sites with a large range in treatment depth,
such as AC-LNI. The purpose of this study is to investigate the clinical applicability of using
mixed energy VMAT plans to treat AC-LNI in comparison to conventional single energy VMAT
plans.
Methods and Materials
Patients
Patients with AC-LNI were considered for this study. The patient demographic was
collected from two clinical sites, and consisted of 20 patients with AC-LNI. The lymph node
systems involved for the patients considered in this study included the external iliac system,
internal iliac system, and inferior mesenteric system. No patients with metastatic disease were
included in this research. All cases included in this research were evaluated retrospectively using
the patient’s CT image collected during the simulation process of their treatment.
 Computed Tomography scans from each patient’s simulation procedure were collected.
All patients were simulated, planned, and treated in the supine position. The CT images were
taken head-first with the scanning field of view (FOV) including the pelvic region, at 3 mm slice
thickness. Patients included from site 1 were simulated on a Siemens Somatom Sensation Open
CT machine, and were immobilized with a Civco Hipfix Thermoplastic positioning tool. Patients
taken from site 2 were simulated on a Philips Big Bore CT machine, and were immobilized
using a Civco Vac-Lok cushions and a Q-Fix indexing tool. Contours were added to each
patient’s CT image for the purpose of this study.
Contouring
Treatment volumes including gross tumor volume (GTV), clinical target volume (CTV)
and PTV were contoured by the radiation oncologist who had treated the patient during their
radiation therapy, while normal structures were contoured by a single medical dosimetrist
responsible for carrying out the planning in this study.. For the purpose of this study, all CTV
volumes include a primary tumor (GTV) with associated lymph nodes. For the PTV, a 1 cm
margin was added to the CTV. Normal structures included in this study were the skin, bladder,
bowel bag, external genitalia or vagina, left femur, and right femur. In cases where the patient’s
CT included contrast in the bowel, the contrast was also contoured to allow for Hounsfield Unit
(HU) corrections.
Treatment Planning
All patients in this study were prescribed a dose of 1.8 Gy daily for 25 fractions for a
total of 45 Gy. This prescription was used for curative intent. All parameters used for creating
the treatment plans in this study (Table 1) remained consistent between patients. All plans were
created for treatments to take place using a Varian TrueBeam 1032 with a multileaf collimator
(MLC) leaf thickness of 0.5 to 1 cm. The algorithm used to perform all optimizations was the
Varian Eclipse Analytical Anisotropic Algorithm (AAA).
Three treatment plans were created for each patient on the Varian Eclipse treatment
planning system, version 15. These plans included one plan using 6 MV photons, one using 10
MV photons, and one plan that used both 6 MV and 10 MV photons. Each of these plans were
created using three complete arcs covering 359° around the patient in the axial plane. The three
complete acrs used in each plan included an arc with a 10° collimator rotation, an arc with a 0°
collimator rotation, and an arc with a 350° collimator rotation.
 The two single energy plans were created with the same setup configurations. Each plan
was made with two counterclockwise (CCW) arcs and one clockwise (CW) arc. The first CCW
arc had a collimator rotation of 10°, with the Y-axis and X1 jaws encompassing the PTV given a
1 cm margin, and the X2 jaw opened 2 cm. The CW arc had a collimator rotation of 0°, with the
Y-axis jaws encompassing the PTV given a 1 cm margin, and the X-axis jaws opened 7.5 cm
each. The second CCW arc had a collimator rotation of 350°, with the Y-axis and X2 jaws
encompassing the PTV given a 1 cm margin, and the X1 jaw opened 2 cm.
The mixed energy 6 MV and 10 MV plan was created by splitting the dose delivered in
each fraction between two separate plans that were then summed together. The 10 MV partial
plan was used as a base dose plan when creating the 6 MV partial plan. This was done so that the
previous dose delivered from the 10 MV partial plan could be taken into account by the
optimizer when creating the 6 MV plan. After the creation of the two partial plans, they were
summed together to create a mixed energy VMAT plan that delivered a total of 45 Gy over 25
fractions. The 10 MV partial plan was created with a prescription of 1.2 Gy over 25 fractions
using one CCW and one CW arc. The CCW arc had a collimator rotation of 10°, with the Y-axis
and X1 jaws encompassing the PTV given a 1 cm margin, and the X2 jaw opened 2 cm. The CW
arc had a collimator rotation of 350°, with the Y-axis and X2 jaws encompassing the PTV given
a 1 cm margin, and the X1 jaw opened 2 cm. The 6 MV partial plan was created with a
prescription of .6 Gy over 25 fractions and optimized using the 10 MVpartial plan as a base dose
plan. This plan using a single CCW arc had a collimator rotation of 0°. The Y-axis jaws
encompassed the PTV given a 1 cm margin, and the X-axis jaws were both opened to 7.5 cm.
Optimization structures were contoured by the medical dosimetrist responsible for
carrying out the planning in this study. The same optimization structures were used for each
plan. Two optimization structures were added to all patient CTs and used during optimization of
the treatment plan. One structure was created by cropping the bowel bag normal structure from
going into the PTV, with a 0.1 cm margin. Similarly, the second structure was created by
cropping the bladder normal structure from going into the PTV, with a 0.1 cm margin.
All treatment plans were optimized to the set prescription dose and referenced specific
OAR constraints. All plans had Normal Tissue Objectives (NTO) set manually. Automatic
intermediate dose was used for each plan. All plans were normalized to the PTV target volume
so that 95% of the PTV received 100% of the prescription dose. Plans were optimized to meet
OAR constraints as proposed by the Radiation Therapy Oncology Group (RTOG).13
Plan Comparisons
The three treatment plan types created for each patient were compared. The three plan
types included the 6 MV photon plan with full prescription dose, the 10 MV photon plan with
full prescription dose, and the mixed energy plan sum created from the 6 MV and 10 MV plans
with partial prescription doses. The plans were compared for OAR sparing, monitor unit (MU)
usage, and PTV coverage
The OAR considered in comparing the 6 MV and 10 MV single energy plans with the
mixed energy plans were chosen based on RTOG standards. The OAR included the bladder,
bowel, and femoral heads. Specific comparison points (Table 1) were included from RTOG 0529
normal tissue tolerances.14
The MUs needed and dose distribution were compared between plan types. The total
MUs for each arc of each plan type were totaled and averaged between patients. The dose
distribution was compared using the conformity index (CI). The dose uniformity was determined
using the homogeneity index (HI).
Results
Various effects of implementing a mixed energy VMAT plan can be seen in the
preliminary results. OAR sparing did not benefit from a mixed energy plan. The 6 MV single
plan produced the best sparing to the bladder. The 10 MV single plan produced the best sparing
to the bowel. Both femurs were spared best by the 10 MV single plan. The number of MUs
needed was lowest on average for the 10 MV plans, but only by a small margin. The mixed
energy plans on average used significantly less MUs than the single energy 6 MV plans. The
percentage of the PTV receiving 100% of the prescription dose was larger for the mixed energy
plan than the single energy plans. The HI demonstrates limited variation between the three plans.
The CI was lower on average for the mixed energy plans than the single energy plans, which
were very similar.
Discussion
The results of this study were not consistent with the research conclusions provided by
Momin et al10 and Shyam Pokharel.11 This study on AC-LNI treatment using mixed energy
VMAT planning did not show that OAR sparing was increased by a mixed energy plan. Unlike
the two aforementioned studies, this research showed that PTV coverage could improve by
implementing a mixed energy VMAT plan. This suggests that the benefits provided in using
mixed energy VMAT plans may depend on the range in depth of the PTV site being treated. This
study additionally investigated the number of MUs used for mixed energy VMAT plans in
comparison to single energy VMAT plans.
Conclusion
Mixed energy plans in VMAT treatment of AC-LNI can affect PTV coverage and OAR
sparing. PTV coverage is greater for mixed energy VMAT plans than for single energy VMAT
plans. Conversely, the OAR sparing decreased for mixed energy VMAT plans when compared to
single energy VMAT plans. This conclusion, which conflicts with studies produced by Momin et
al10 and Shyam Pokharel11, may be a result of the method for normalizing the 10 MV and 6 MV
partial plans before the two partial plans were summed.
Through the results of this research, certain limitations were observed and areas needing
further investigation were noted. This study was limited by the number of patients available for
retrospective treatment planning. Only twenty patients were able to be included in this study due
to a lack of patients previously treated with AC-LNI from the sites providing patient CT images.
Further research into this topic could be done to advance the clinical understanding of mixed
energy VMAT treatments for AC-LNI. This study focused on the primary treatment of a AC-
LNI radiation therapy prescription, which would typically include an additional boost
treatment.15 More research is needed to assess the effects of implementing mixed energy VMAT
planning with both the primary and boost treatments in AC-LNI treatment.
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 Tables

Table 1. Dosimetric constraints for OAR considered in optimization.14

OAR Dosimetric Constraint

No more than 50% above 35 Gy

Bladder No more than 35% above 40 Gy

No more than 5% above 50 Gy

No more than 50% above 30 Gy

Femoral Heads No more than 35% above 40 Gy

No more than 5% above 44 Gy

No more than 50% above 30 Gy

Iliac Crests No more than 35% above 40 Gy

No more than 5% above 50 Gy

No more than 50% above 20 Gy

External Genitalia No more than 35% above 30 Gy

No more than 5% above 40 Gy

No more than 50% above 35 Gy

Bladder No more than 35% above 40 Gy

No more than 5% above 50 Gy

No more than 200 cc above 30 Gy

No more than 150 cc above 35 Gy

Bowel
No more than 20 cc above 45 Gy

None above 50 Gy