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Jessica Ezelle
April Case Study
April 9, 2017
Pediatric Ewings Sarcoma per Protocol AEWS 1221
History of Present Illness: Patient WA is a 5-year-old white male who presented in September
2016 with right leg swelling, one of the most common symptoms of Ewings Sarcoma. 1 WA then
underwent an MRI evaluation on September 5, 2016 that revealed a large lobulated enhancing
and predominantly solid mass, involving the distal half of the right thigh and arising from the
lower end of the adductor magnus muscle and the musculotendinous joint. This mass
predominantly involved the posterior and posterior-medial compartment of the right thigh, which
encased more than two-thirds of the distal superficial femoral vessels. This femoral involvement
was concluded due to the lack of a fat plane between the mass and femoral cortex. The lower end
of the mass extended up to the popliteal fossa.
On September 8, 2016, a biopsy of the right thigh was conducted revealing Ewings
Sarcoma/Primitive neuroectodermal tumor (PNET). To further work up WAs tumor staging he
then underwent a right groin lymph node biopsy on September 14, 2016 which was negative for
malignancy. Groin lymph node involvement is usually very rare with Ewings Sarcoma. 1 To
further determine WAs tumor involvement, the patient underwent a bone-marrow biopsy, which
also returned negative for malignancy. Once his work up was complete it was concluded that
WA has stage IV Ewings Sarcoma of the right distal thigh.
Past Medical History: WA has a past medical history of a left buttock area abscess drainage
from June 29, 2012. He had a port placement September 16, 2016. He is positive for Methicillin-
resistant Staphylococcus aureus (MRSA) infection colonization, meaning the patient carrys the
MRSA virus but does not have an active virus. WA is also reported to have anemia,
thrombocytopenia and to have undergone, and is currently undergoing chemotherapy.
Chemotherapy: Due to WAs treatment for this Ewings Sarcoma being per protocol
AEWS1221 he was treated with a strict chemotherapy regimen. For each chemotherapy session
WA was admitted to the childrens hospital. WAs initial chemotherapy began September 16,
2016. His usual course of chemotherapy was as follows: Vincristine day 1, Doxorubicin with
Dexarazoxane on days 1 and 2, Cyclophosphamide on day 1 with MESNA, followed by
Neupogen on day 3.
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The Protocol: Patient WA was on regimen A of Protocol AEWS1221 which consisted of 4

phases of therapy: induction, local control, consolidation, and metastatic irradiation. Induction
component lasts 12 weeks, the patient receives 6 cycles of chemotherapy every 14 days with the
chemotherapy plan mentioned earlier. Local control for all patients will take place once the
patient recovered from the induction phase, usually around week 13. Local control can be
surgery, radiation or combination of both. For patients, such as WA, receiving radiation alone,
radiation should begin in conjunction with the next phase of the trail, consolidation.
Consolidation lasts 16 weeks, with 8 cycles of the standard chemotherapy, as discussed earlier,
every 14 days. Once the patient has recovered from their consolidation chemotherapy then they
can begin their radiation on their metastatic disease. In patient WAs case this would be when his
lung would receive radiation.2
Social History: WA lives at home with his mother, father, maternal grandmother, and 16-year-
old sister. He also has two siblings who are away at college. One of WAs sister has downs
syndrome. There is no family history of primary or secondary relatives with cancer.
Medications: WA uses the following medications: Ranitidine (for acid reflux), Benadryl,
Filgrastim (a bone marrow stimulant), Polyethlene glycol (for constipation),
Sulfamethoxazole/trimethoprim (an anti-biotic taken only on Saturday and Sunday), Zofran (for
nausea and vomiting), Calcium carbonate gum (for stomach discomfort), Lidocaine-prilocaine
cream (as needed for injection or port access). There were no known reported medical allergies.
Diagnostic Imaging: An MRI on September 5, 2016 revealed a large lobulated enhancing and
predominantly solid mass involving the distal half of the right thigh, arising from the lower end
of the adductor magnus muscle and the musculotendinous joint and extending to the popliteal
fossa. A CT scan was performed on September 15, 2016 of the chest and abdomen revealing
bilateral small pulmonary nodules with the largest nodule in the left lower lobe measuring 4.2cm
x3.5 mm with a small amount of calcification. A subtle soft tissue abnormality was noted
anterior to the 11th rib costovertebral junction correlating with a focal area of increased activity
found on PET/CT. A PET/CT was performed on September 15, 2016 revealing multiple punctate
soft tissue bilateral nodules in the lungs with the most predominate nodule being in the lower left
lung. They did not show appreciable metabolic activity but were under the threshold to do so.
After the first stage of chemotherapy there was a restaging MRI on December 7, 2016. This MRI
revealed interval decreased size of posterior compartment in the right thigh measuring 3cm x
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1cm x5 cm compared to its original size of 8.2cm x6.2cm x10 cm before chemotherapy. Another
PET/ CT was performed on December 9, 2016 that revealed interval resolution of the
hypermetabolic soft tissue mass within the musculature of the right thigh consistent with
excellent therapeutic response.
Radiation Oncologist Recommendations: Since Patient WA was being treated per the Protocol
AEWS1221 with his medical oncologist, the radiation oncologist continued to follow suit and
treated him with radiation therapy per the protocol also. The patients radiation therapy was to
begin in conjunction with the second phase of his chemotherapy, consolidation. WA was to
receive a total dose of 55.8 Gy with an initial field receiving 45 Gy and a boost field of 10.8 Gy
each in 1.8 Gy fractions per day. Regarding the patients pulmonary metastatic disease, a
frequent hematogenous metastatic disease site, the radiation oncologist will speak with WAs
medical oncologist whether this should be taken care of with surgery and radiation or radiation
alone.1 On this protocol, patients less than 6 years-old would receive a whole lung dose of 12 Gy
in 1.5 Gy fractions and a boost to a planning target volume (PTV) of an additional 36 Gy in 1.8
fractions. The radiation oncologist felt that the metastatic site involving the left posterior chest
wall at the 11th rib has shown complete response to treatment but a dose of 50.4 Gy could be
utilized because it appears to have been non-osseous.
The Plan: The initial plan was a 3D conformal plan consisting of 2 beams, a left anterior oblique
(LAO) and a right posterior oblique (RPO). This plan is to be treated in 25 fractions in 1.8Gy
daily fractions. The dosimetrist normalized the plan to the 95% point dose to achieve better
coverage around the PTV. The total dose to this plan was 45 Gy. Following the initial plan the
radiation oncologist ordered a boost which was also a 3D conformal plan that consisted of the
same two beams that the initial plan had, a LAO beam and a RPO beam. However, the field size
was condensed on the boost field. The boost plan consisted of 6 total fractions at 1.8 Gy per
fractions to a total dose of 10.8 Gy. The medical dosimetrist normalized this plan to the 100%
point dose. Upon completing both the initial and boost plans, the total dose to the right thigh
would total 55.8 Gy.
Patient Set-up/Immobilization: The patient was brought into the CT simulation room and
placed on the CT table where he was then set-up under general anesthesia with Propofol used to
sedate him. Propofol is generally the sedation medication of choice for treatments and
simulations because of its average waking time of 7-8 minutes allowing for a quick recovery
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every day.3 WA was placed supine with a pillow under his head. Velcro straps were placed
around the patient and the table to help make sure that the patient would not roll off the table. A
Vac-Loc was made for WAs lower body from his waist down to immobilize his legs during
treatment. Arbitrary marks were placed on the patients hips for leveling purposes with paint
marker then a fiducial marker was placed on top as that the marks so that they may be seen in the
treatment planning system (TPS) and the shifts to the correct isocenter could be calculated for
treatment. Long lines were drawn down the patients leg to help with straightening of the leg on
a daily basis in the treatment room. The patient was then scanned on the CT scanner and the scan
was sent to the TPS.
Anatomical Contouring: Once the CT scan was transferred into the Phillips Pinnacle Radiation
TPS, it was then fused with WAs PET/CT scans from September 15,2016 and December 9,
2016. The radiation oncologist used the original PET/CT before chemotherapy from September
to contour his GTV for the initial plan to 45 Gy. The gross tumor volume (GTV)45Gy was then
expanded by 1cm to create a clinical target volume (CTV)45Gy and the CTV was then expanded
by .5cm to create the PTV45Gy, the total margin to be prescribed to, to allow for uncertainties in
treatment set-up. Then the radiation oncologist created a GTV for the boost plan. For this he used
the PET/CT from December, post-chemotherapy disease. After the Radiation Oncologist created
his GTV2, it was then expanded by 1cm to create CTV2 and from CTV2 it was expanded by
.5cm to create GTV2 for the boost to 10.8 Gy. The only other anatomical body parts that were
contoured were the external anatomy of the patient and the patients femur.
Beam Isocenter Arrangement: The beam isocenter was automatically placed via the TPS in the
center of the PTV45Gy contour then adjusted slightly to created more even shifts for the
therapists on the machine. With this being a 3D plan, the medical dosimetrist carefully placed an
LAO beam and RPO beam so that they encompassed the GTV volume yet did not interact with
the patients opposing leg. The radiation oncologist asked for a field block of .7mm around the
GTV using multi-leaf collimator (MLC) leaves. The medical dosimetrist had to be careful not to
include too much of the epiphyses, or growth plates, of the bone in the field to try not to interfere
with the patients growth. However, most Ewings Sarcomas typically develop in the long bones
around their growth plates.4 The medical dosimetrist chose a two-beam arrangement using an
LAO beam of 60 and RPO beam of 240 both using 6MV energies, making sure to keep as
much healthy tissue out of the field as possible to ensure good lymphatic flow and avoid limb
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edema.5 The medical dosimetrist used a calculation point to prescribe her dose to help optimize
her dose distribution in their field. The dosimetrist used control points in her plan to help cool
bring the hot spots down.
The boost plan was created off of the same CT data set with smaller fields correlating to the
smaller drawn PTV2 also utilizing a .7mm margin MLC block. The block difference in the fields
from the initial plan to the boost plan were 10cm x14cm to 7cm x15.5cm respectively. The boost
plan utilized the same beams as the initial plan, a LAO beam at 60 and a RPO beam at 240.
Both beams were still treated using 6MV energies and control points to help cool off the plan.
The initial and the boost plan were both to be treated on a Varian 23IX with On Board Imaging
(OBI). The patients prescription called for a weekly cone beam cat scan (CBCT) and daily
kilovoltage (kV) orthogonals to verify the patients setup before treatment began.
Quality Assurance: The MUs calculated by the TPS were double checked in Diamond, a third-
party MU calculation software. The tolerance between the TPS and Diamond MU must be within
5% and all of the patients fields within their tolerances. After the plan was fully uploaded into
the Mosaiq treatment system including the printed plan document and printed Diamond monitor
unit calculation verification. The radiation physicist does a double check on the plan to ensure
that everything is correct and then signs off on the plan. Before the patient is treated, the
radiation therapists also do a chart check of the patients chart to ensure what is printed from the
TPS matches what is imported into Mosaiq, since what is in Mosaiq is what will be delivered to
the patient.
Conclusion: There are always a couple of challenges when treating extremities especially in
young children. In this setup, the dosimetrist had to make sure that the contralateral leg did not
receive any dose, and that as much health tissue as possible was spared from lymphatic purposes.
This patients tumor came close to the epiphysis or growth plate of his femur so that was a
challenge to treat all of the PTV and spare as much of the epiphysis as possible to not interfere
with the patients growth. Although the patient was not on Protocol AEWS1221, he was treated
per the protocol so the medical dosimetrist had to be sure that their work was done in a timely
manner so that it fell in conjunction with the patients chemotherapy timing. Another challenge
of this treatment was trying to keep the treatment time to a minimum due to the fact the patient
was to be sedated every day for treatment and the less amount of time the patient is under
sedation the better it is for the patient. Although control points help cool off a plan there cannot
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be too many because it will increase the treatment time on the table. It can be tedious to plan a
soft tissue extremity in general but when it involves children there becomes even more to think
about and analyze in planning.
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References
1. Chao KS, Perez C, Brady L. Bone and Ewings sarcoma. In: Radiation Oncology
Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams, & Wilkins;
2011:697
2. AEWS1221: Randomized Phase II Trial Evaluating the Addition of the IGF-1R
Monoclonal Antibody Ganitumab to Multi-agent Chemotherapy for Patients with Newly
Diagnosed Metastatic Ewing Sarcoma. The Childrens Oncology Group Website.
https://www.childrensoncologygroup.org/index.php/aews122. Accessed March 8, 2017.
3. Machata A, Willschke H, Kabon S, Kettner S, Marhofer P. Propofol-based sedation
regimen for infants and children undergoing ambulatory magnetic resonance imaging. Br
J Anaesth. 2008;101(2): 239-243. http://dx.doi.org10.1093/bja/aen153. Accessed March
8, 2017.
4. Batista N, Dea N, Fisher C. Assessment and treatment of primary milagnant tumors of
the axial skeleton. In Winn, RH, ed. Youmans & Winn Neurological Surgery e1. 7th ed.
Philadelphia, PA: Elsevier; 2017: 2421-2427.
5. Khan F, Gerbi B. Pediatric malignancies. In: Treatment Planning in Radiation Oncology.
3rd ed. Philadelphia, PA: Lippincott, Williams, & Wilkins; 2012:666.
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Figure 1. Patient set-up with pillows and vac-loc in CT simulation.

Figure 2. Patient AP set-up picture with lines down leg to keep a consistent straightness.
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Figure 3. Isocenter placement for both the initial and boost plan.
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Figure 4. Isocenter marked in axial plane for the initial plan with the PTV45.
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Figure 5: Marked isocenter in the sagittal plane for the initial plan with the PTV45.
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Figure 6. Marked isocenter in the coronal plane for the initial plan with the PTV45.
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Figure 7. LAO and RPO fields for the initial plan with the PTV45 with MLC blocking.
.

Figure 8: The Dose Volume Histogram (DVH) for the initial plan to 45 Gy.
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Figure 9. Marked isocenter in the axial view for the boost plan with the PTV2.
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Figure 10. Marked isocenter in the sagittal view for the boost plan with the PTV2.
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Figure 11. Marked isocenter in the coronal view for the boost plan with the PTV2.
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Figure 12. LAO and RPO plans for the boost plan with the PTV2 with MLC blocking.

Figure 13: The DHV for the Boost plan to 10.8 Gy.
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Figure 14. Marked isocenter in the axial view of the initial and boost composite plan with the
PTV45 in the lime green color and the PTV2 in the light blue.
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Figure 15. Marked isocenter in the sagittal view of the initial and boost composite plan with the
PTV45 in the lime green color and the PTV2 in the light blue.
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Figure 16. Marked isocenter in the coronal view of the initial and boost composite plan with the
PTV45 in the lime green color and the PTV2 in the light blue.
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Figure17. Composite DHV for both the initial and boost plans: