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Ryan Pohl
04/09/17
DOS 711: Research Methodology

Brain SRS: 7-Site, Single Isocenter Treatment

History of Present Illness: Patient ER is a 69-year-old Caucasian female that presented with
metastatic disease to 7 separate sites in her brain. She entered radiation consultation with a
history of oligometastic (stage IV) non-small cell lung cancer. In December of 2015 she
developed vague symptoms that were consistent with bronchitis. She was given antibiotics, but
continued to have a lingering cough with shortness of breath. Shortly after, ER received chest x-
rays that were negative for any major abnormalities. However, the cough persisted and in May
of 2016 she underwent a CT chest scan that showed a 1.7cm x 1.1cm right adrenal nodule and a
3.8cm x 3.2cm left hilar mass that was highly suspicious for malignant activity. A PET scan
followed that confirmed a mass in the left infrahilar area with a standardized uptake value
(SUVmax) of 17.1 (indicating high level of metabolic activity). A bone scan was completed and
found to be unremarkable. Afterward, an MRI of her head showed a subcentimeter concentration
of contrast enhancement in the right inferior frontal gyrus. This discovery was considered a
vascular abnormality as it did not have characteristics typical of a metastatic lesion. ER then
underwent an endobronchial ultrasound (EBUS) and the resulting biopsy of an interlobar lymph
node was positive for metastatic poorly-differentiated carcinoma. A biopsy of the right adrenal
gland also confirmed adenocarcinoma. In June 2016, she started chemotherapy using
carboplatin-pemetrexed and ended up receiving 4 cycles. Concurrently, her left lung mass was
treated with radiation to 6600 cGy using a 5-field IMRT technique. In September 2016, a
fludeoxyglucose (FDG) PET/CT was conducted that showed a decreased SUVmax (now 4.8) of
the primary infrahilar tumor. However, the metastatic right adrenal nodule grew to 2.1 cm x 3.6
cm and a 0.8cm nodule was discovered in her the right ischiorectal fossa. Following this scan,
patient ER received a right adrenalectomy and a course of radiation to her right ischiorectal fossa
consisting of 5000 cGy using a conformal arc technique. A follow-up MRI (with and without
contrast) was performed in February 2017 and multiple enhancing metastases in right frontal
lobe, bilateral occipital lobes, left temporal lobe, and midline pons were found.
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Past Medical History: Patient ERs past surgical history includes a left breast lumpectomy in
1979 and septoplasty in 2015. She developed adhesive capsulitis of her right shoulder in 2006
and osteoporosis in 2009. In 2017, she experienced paroxysmal atrial fibrillation that is likely
linked to her chemotherapy and an esophageal injury that is likely linked to previous radiation
treatment. ER reports situational anxiety and reactive depression that dates back to 2010.

Social History: Patient ER has 6 sisters and a brother. She is a retired emergency room and
intensive care unit nurse who participated in recreational dance. When in nursing school, she
would travel to class every day via an underground tunnel along with a group of classmates. She
suspects they may have been exposed to asbestos or another chemical and reported that 3 of her
classmates were also diagnosed with lung cancer. Patient ER went through a 5-year period
where she smoked half a pack of cigarettes a day, but quit smoking in 1961. She reported no
current drug, alcohol, or smokeless tobacco use. Her father was a former senator who died at age
92 due to atrial fibrillation and her mother passed at age 84 from coronary artery disease. She
has a brother who was diagnosed with leiomyosarcoma and several sisters with histories of
breast cancer.

Medications: Patient ER uses the following medications on a daily basis: acetaminophen


(Tylenol extra strength), albuterol, alprazolam (Xanax equivalent), apixaban, budesonide-
formoterol, diltiazem, lidocaine-prilocaine, lorazepam, metoclopramide, omeprazole,
ondansetron, oxycodone, oxycontin, peg electrolyte, senna-docusate, sertraline (Zoloft
equivalent), simethicone, and a multivitamin.

Diagnostic Imaging: Patient ER has had over 30 imaging procedures conducted, but 3 scans in
particular were instrumental in diagnosing her diseases. Her primary lung tumor was discovered
in a CT scan performed in May of 2016. This CT scan was implemented as a response to a
lingering cough that spanned approximately 5 months. In September 2016, after receiving
radiation treatment to her left lung, ER received a FDG PET/CT that showed a 0.8cm nodule in
her right ischiorectal fossa. In February 2017, following treatment of the right ischiorectal fossa,
an MRI on her brain revealed 7 metastatic tumors. This scan also indicated that there was a
moderate amount of vasogenic edema in several of the lesions. In addition to diagnostic
imaging, a stereotactic MRI was used to aid in planning of the SRS.
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Radiation Oncologist Recommendations: With 7 metastatic cancer sites located in patient


ERs brain, the radiation oncologist was left with limited options. The first option discussed with
ER was to forego any treatment or any medical management practices (including the use of
steroids or anti-seizure medications). With no treatment, the cancer would continue to grow; this
could cause neurological problems and likely lead to neurologic death. The radiation oncologist
recommended ER undergo a course of radiation therapy. He explained that standard treatment
for brain metastasis included whole brain irradiation followed by a stereotactic radiosurgery
(SRS) boost. This would involve a daily treatment, Monday through Friday, for 2 weeks. The
patient would take a week break, get a specialized stereotactic brain MRI, and end this course
with an SRS boost to the sites of metastasis. The other option presented to ER was SRS alone
with close surveillance of the treatment site and, if needed in the future, re-treatment using whole
brain irradiation. If getting SRS alone, the treatment would be delivered in a single day. Either
radiation treatment option would require follow-up brain MRIs every 3 months to monitor for
progression or new metastatic sites. The physician then explained that neurocognitive symptoms
such as memory loss, inability to concentrate, and motor function decline are more common with
whole brain radiation compared to SRS alone. After considering these factors, patient ER
elected to pursue a single SRS treatment.

The Plan (prescription): The radiation oncologist recommended that patient ER receive
radiation treatment to all 7 metastatic brain lesions using an SRS technique. He determined that
the best course of action was to deliver 1500 cGy to the pons PTV and 2200 cGy to the 6 other
sites. In the treatment planning system (TPS), 1500 cGy was entered as the prescribed dose and
dose-shaping structures (sometimes referred to as rings or dummy structures) were created
by the planner to direct doses of 2200 cGy to the other PTVs. In order to achieve adequate
coverage, the dose was prescribed to the 61.0% isodose line. This created extreme hotspots that
were around 175% of prescribed dose, but the plan was considered acceptable because these
hotspots were positioned within PTVs. Patient ERs treatment was designed to be delivered in a
single fraction.

Patient Setup/Immobilization: The goal of patient setup and immobilization is to create a


position that is both reproducible and comfortable. For CT simulation, patient ER was
positioned head-first into the scanner and supine with a cushion placed under her knees to
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alleviate stress put on her lower back (see figure 1). A slant board/base plate with a B2 block and
reinforced 3-point thermoplastic mesh face mask was used to immobilize ERs head.
Thermoplastic mesh is a customizable material that molds to a patients facial structure and is
used to create a reproducible setup. In order for a treatment plan to be accurate, the patient needs
to be oriented in the same exact position for treatment as they were for the CT simulation scan.
ER was aligned with in-room lasers and given intravenous (I.V.) contrast. The I.V. contrast (100
cc omnipaque) was used to enhance blood vessels and improve visualization of these tissues
during the contouring process. Radiopaque BBs were placed on the anterior and lateral surfaces
of the mask to make a reference point for treatment planning. During the planning process, this
reference point was used to determine the couch shifts necessary to move ER to an established
treatment isocenter. Since the treatment region would encompass small but significant
structures, the CT scan captured images at intervals of 1.25 mm.

Anatomical Contouring: After completing the CT simulation scan, the axial images were
transferred to MIM software to be fused with an MRI. The radiation oncologist used this fusion
to help delineate all necessary planned target volumes (PTVs) and surrounding organs at risk
(OR). After the CTVs were identified on the CT images, a 1 mm expansion around the CTVs
was created to make the PTVs. This margin coincides with specifications set in AAPM Reports
40 and 45 to ensure linac isocenter accuracy is within 1mm.1 ERs metastatic sites were rather
evenly spaced out with one PTV in each of the following regions: the pons, the left parietal, left
occipital, left temporal, right parietal, right temporal, and right frontal lobes of her brain. The OR
that were contoured include: brain, eyes, lens, optic apparatus (optic nerves and chiasm), and
brain stem. The radiation oncologist then reviewed the prescription plan with the medical
dosimetrist and gave them a set of dosimetry goals. The aim of this treatment was to deliver
95% of the prescribed dose to all of the PTVs while keeping dose to eyes and lens less than 1000
cGy, dose to optic apparatus less than 800 cGy, and dose to the brainstem less than a 0.03cc
hotspot of 1500cGy (for areas outside of pons PTV). The dosimetrist uploaded the physician
contours and dataset to Eclipse version 11 TPS and proceeded to design ERs 7-site, single
isocenter, SRS treatment plan.

Beam Isocenter/Arrangement: Patient ER was treated on a Varian TrueBeam (SN 2519) linear
accelerator using 10 MV flattening filter free (FFF) photon beams. Using 10FFF decreased
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treatment time because it could deliver at a dose rate of 2400 MU/min. Having a shorter delivery
timeframe increased the treatments precision by reducing the probability of intrafractionary
motion. Another benefit of removing the flattening filter is a decrease in scatter radiation
delivered outside of the field. This machine is also equipped with a 120 multi-leaf collimator
(MLC) system and a Varian PerfectPitch 6 degrees of freedom (6DoF) couch. Compared to a
standard treatment couch, the 6DoF couch allows for a higher level of image guided accuracy
because it includes two additional axes of rotation (pitch and roll). This assured the patients
treatment position had the same coordinates as the CT simulation. Without the 6DoF couch, for
every centimeter between the isocenter and target, an additional 0.35mm margin is required to
account for 95% of rotational uncertainties at initial setup.2 The planner placed isocenter at the
coordinates of x-0.28cm, y-3.48cm, and z-0.95cm, which was close to the center of patient ERs
brain. This location was determined by looking at an orthogonal view and visually placing
isocenter at the geometric center of the targets. Patient ER was treated with a VMAT technique
that utilized 4 arcs. The first field was a coplanar arc that rotated clockwise from a gantry angle
of 181 to 179 with a collimator rotation of 290. The second arc rotated counter-clockwise
from gantry 179 to 350, had a collimator rotation of 350, and a couch rotation of 45. The
third arc had a gantry rotation that also travelled counter-clockwise but from 10 to 181 with a
collimator rotation of 295 and a couch rotation of 315. The final arc was a vertex field that
rotated clockwise from gantry angle 181 to 10, had a collimator rotation of 350, and a couch
rotation of 270. In order to create the appropriate field sizes, the planner first combined all 7
PTVs into one Boolean structure labelled PTVtotal. Then, the dosimetrist used the Fit to
Structure tool to add MLCs that covered PTVtotal with a 0.3cm margin. This process was only
used to help set an appropriate field size; after field size was established the MLCs were deleted.
Collimator rotation was also adjusted to avoid island blocking (see figure 2) and to maximize
blocking between targets as the gantry rotated.

Treatment Planning: The planner for this particular treatment used a technique developed by
the University of Alabama at Birmingham (UAB).3 Variations of this technique have been used
to successfully treat as many as 9 separate metastatic brain sites with a single isocenter. In
general, cases with more metabolic sites will require a greater number of beams to achieve
adequate coverage for all PTVs. For instance, most cases with only 4 separate PTVs were able
to obtain dosimetric goals using 1 full coplanar axial arc and 1 non-coplanar vertex arc. Patient
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ERs 7-site SRS plan consisted of 4 VMAT arcs: 1 full coplanar axial arc and 3 non-coplanar half
rotation arcs that were equally spaced in the superior hemisphere of her brain (see figure 3). Her
treatment plan was designed on Eclipse Version 11 and utilized Analytical Anisotropic Algorithm
(AAA) as the dose calculation algorithm. It was designed for a Varian TrueBeam (SN 2519)
linear accelerator using beam energies of 10FFF. Trials conducted with 6FFF photon beam
energies produced almost identical results, but could only deliver at a dose rate of 1400 MU/min.
Energies of 10FFF were chosen because they have a maximum dose rate of 2400 MU/min and
would, therefore, reduce treatment time. The first step the dosimetrist took to plan this case was
to evaluate the planning targets drawn by the physician. The general rule of thumb outlined by
UAB was if any PTV had a volume less than 3 cubic cm then the planner should decrease the
calculation grid size to 0.1cm. Patient ER had several PTVs under 3 cubic cm so this change was
implemented. Next, the planner used the Boolean Operator function to combine all of the PTVs
in one structure labelled PTV_total. In order to conform dose around each PTV, a set of 3
concentric rings were created around each target. The inner ring had a thickness of 3 mm, while
the middle and outer rings had a thickness of 4 mm each. The 4 VMAT arcs were then added
and their isocenter, collimator rotation, and field sizes adjusted to appropriate settings. The
following optimization objectives were then set in Eclipse: each individual PTV was given a
lower objective with priority 100 for the target to receive 102% of the prescribed dose, the inner
rings were given upper objectives with priority 150 to receive less than 98% of the dose, the
middle rings were given upper objectives with priority 100 to receive less than 50% of the dose,
and the outer rings were given upper objectives with priority 80 to receive less than 40% of the
dose. A Brain-PTVs mean constraint with priority 100 was set to 250 cGy and the normal
tissue objective (NTO) was left unchecked. The plan was normalized so all targets received
100% of prescribed dose to 99% of their volume. The results of these plan settings were then
evaluated by calculating the conformity index (CI) of each target. The CI for each PTV was
determined by dividing the volume of the body with 100% prescribed dose by the volume of
each PTV with 100% prescribed dose. A CI of 1 means the plan is perfectly conformal but a
realistic goal is to achieve less than 1.5. Patient ERs treatment plan produced the following CI
results: left parietal had 1.7, left occipital had 1.07, left temporal had 1.10, right parietal had
1.21, right temporal had 1.16, right frontal had 1.09, and pons had 1.06. The plan met all
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dosimetric goals set by the physician and was turned over to the physics staff for Quality
Assurance (QA).

Quality Assurance/Physics Check: There were two primary checks used to ensure the
accuracy of this particular SRS plan: ArcCHECK and trajectory logs. ArcCHECK, developed by
Sun Nuclear, uses a cylindrical phantom with a diode array to measure dose fluence. The
phantom is 27cm in diameter and has diodes spaced 1cm apart at an effective depth of 3.3cm.
The measured dose fluence can be compared to its calculated values to check for any
discrepancies in the dose matrix. For patient ERs plan, there were 865 diode measurements
made and 99% agreed within 3% or 3mm. Four absolute dose point measurements were
compared with the planning systems calculations in regions of uniform, high dose. The ratio of
calculated dose to measured dose for the four locations were 1.00, 0.97, 1.01, and 0.98. Analysis
of ArcCHECK information produced a satisfactory agreement between planned and measured
values. Trajectory logs kept track of where MLCs were supposed to be and compared them
where it was during actual treatment. The treatment fields passed all criteria and had a maximum
95th percentile error of 0.05mm. Additional tests were conducted to verify the dosimetric and
spatial position accuracy of the treatment machine. A Winston-Lutz test was conducted to verify
isocenter shift was less than 1mm. There were several measurements taken to confirm the
precision of the systems image-guiding modalities. An ExacTrac system was used to set a
Rando Phantom head at 3 different isocenters and then CBCT was used to double-check its
alignment. This process was then reversed and both trials indicated an agreement better than
1mm for the two modalities.

Conclusion: This particular case was examined because patient ER was treated using a fairly
novel treatment planning technique. There have been a number of similar cases that followed
and this technique appears to consistently produce impressive plans. Its not a complicated
procedure to follow and the plans seem to perform well in QA testing. This technique shows
promise and is able to meet tight dose constraints. Tumors that were not accessible a few short
years ago, can now be successfully treated. The clinical impact of this technique still needs to be
followed closely and measured in the coming years, but it is very exciting to see that this type of
plan is an option. It will be interesting to see how this technique develops and if it can be
modified to treat additional sites such as lung, liver, or spine tumors. Technology involved in
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radiation oncology has made tremendous strides; being able to focus our radiation in seven
different spots in a relatively short timeframe is quite amazing and inspiring.
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References

1. Khan FM, Gibbons JP. The Physics of Radiation Therapy. 5thPhiladelphia, PA: Lippincott
Williams & Wilkins; 2014
2. Stanhope, Carl et al. Physics considerations for single-isocenter, volumetric modulated arc
radiosurgery for treatment of multiple intracranial targets. Practical Radiation Oncology 6.3
(2016): 207-213. http://dx.doi.org/10.1016/j.prro.2015.10.010

3. Dempsey K, Smith H. Technique for plan quality and efficiency using VMAT radiosurgery for
patients with multiple brain metastases. University of Alabama at Birmingham: Department of
Radiation Oncology, 2017.
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Figures

Figure 1: Patient setup and immobilization

Figure 2: Example of collimator rotation that avoids "island blocking".


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Figure 3: Beam arrangement with isodose lines show in axial slice (top left), coronal slice (bottom
left), and sagittal slice (bottom right)

Figure 4: Left temporal PTV with isodose lines shown in axial slice (top left), coronal slice (bottom
left), and sagittal slice (bottom right)
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Figure 5: Left occipital PTV with isodose lines shown in axial slice (top left), coronal slice (bottom left),
and sagittal slice (bottom right)

Figure 6: Dose-volume histogram (DVH) showing relationship of absolute dose received by percent of
structure volume.
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Figure 7: Dose-volume histogram (DVH) showing relationship of absolute dose received by percent of
structure volume.

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