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Ian Zoller
April Case Study
April 9, 2017
Hybrid Planning in Esophageal Cancer
History of Present Illness: The patient, JE, was a 66 year-old man who in December of 2014
began experiencing dysphagia with solid foods. The dysphagia later progressed to difficulty
with liquids and resulted in weight loss of 15-20 pounds over the course of a month. A CT of the
chest was taken on December 23, 2014, which showed irregular thickening of the lower
esophagus at 1.5 cm in thickness and over 5 cm in length. On December 26th, JE underwent an
EGD which revealed an ulcerating esophageal lesion approximately 12.2 cm in length with likely
extension into the stomach. Biopsy taken from this exam revealed moderately differentiated
adenocarcinoma of the distal esophagus. The patient was then referred to the James Cancer
Hospital for consultation.
After meeting with surgery on January 12, 2015, the patient underwent further diagnostic testing
for staging. On January 15th, a PET scan was completed showing increased uptake in the
esophageal mass. In addition, abnormal uptake was reported in the lymph nodes surrounding the
gastrohepatic ligament. On the same day, an endoscopic ultrasound (EUS) was performed
showing a partially obstructing tumor extending 29-40 cm past the incisors with a total length of
14 cm. The tumor was staged T3N1M0 following these exams. On January 21st, the patient met
with medical oncology and radiation oncology to discuss the roles of chemotherapy and radiation
therapy. After reviewing the patients history and diagnostic imaging, the radiation oncologist
recommended neoadjuvant chemoradiation therapy followed by esophagectomy. The patient
was also presented with the option of enrolling in the clinical trial Cancer and Leukemia Group
B (CALGB) 80803. This trial examines the role of induction chemotherapy followed by PET-
directed radiation and esophagectomy. After discussing the logistics of both options along with
the side effects associated with radiation therapy, the patient was consented and enrolled in
CALGB 80803.
Past Medical History: JE presented with a relatively short past medical history including:
gastroesophogeal reflux disease, diverticulitis, diverticulosis, gout, and psoriasis. According to
Bussman,1 chronic GERD is one of the most common etiologic risk factors in patients with
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esophageal cancer. The patient did not report any surgical history prior to the EGD performed
on December 26, 2014.
Social History: JE, a retired jeweler, was married with three children. Before quitting in 2012,
he previously had a 50+ pack year smoking history as well as a history of alcohol abuse. These
two factors are major contributors in the development of esophageal cancer.1 The patient also
reported having a familial history of cancer. The patients mother was diagnosed with colorectal
cancer and the father had been diagnosed with gall bladder cancer; both were 80 years of age at
diagnosis. In addition to the malignancy, the patients father had a history of diabetes,
myocardial infarction, and coronary artery disease.
Medications: The patient reported using the following medications at the time of consult:
Loperamide, Testosterone Cypionate, Citalopram, and Odansetron.
Diagnostic Imaging: After presenting with dysphagia, the patient underwent a CT scan in late
December of 2014 that showed irregular thickening of the distal esophagus. On December 26th,
an EGD was performed showing a lesion 12.2 cm in length and was biopsy proven to be
moderately differentiated adenocarcinoma. After surgical consultation at the James Cancer
Hospital, the patient additionally had an EUS and a PET scan completed on January 15, 2015 to
assist with American Joint Committee on Cancer (AJCC) staging. The PET scan indicated
increased uptake in the region of the tumor and lymph nodes surrounding the gastrohepatic
ligament. The EUS in combination with the PET scan determined the staging to be T3N1M0.
Radiation Oncologist Recommendations: The radiation oncologist presented the patient with
multiple treatment recommendations. The first was for the patient to undergo neoadjuvant
chemoradiation followed by esophagectomy. The prescribed dose would have been 50.4 Gy in
1.8 Gy fractions for a total of 28 fractions and was based on CALGB 9781. The second option
was to enroll in the clinical trial CALGB 80803. The primary objective of this trial was to
examine the role of induction chemotherapy prior to neoadjuvant chemoradiation and
esophagectomy in achieving complete pathologic response. The trial consisted of two induction
chemotherapy arms with group one receiving 3 cycles of modified Folfox 6 and group two
receiving 2 cycles of Carboplatin and Paclitaxel. Following induction chemotherapy, patients in
the trial then began adjuvant chemotherapy targeted to areas of increased uptake in a
prechemotherapy PET scan.2 JE chose to enroll in CALGB 80803 and provided informed
consent.
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The Plan (prescription): Following randomization, the patient was placed in the induction
chemotherapy arm receiving 2 cycles of Carboplatin and Paclitaxel prior to starting
chemoradiation. The patient also received concurrent Folfox during the course of radiation.
Following the criteria for the protocol, the radiation oncologist prescribed a dose of 50.4 Gy to
be delivered in 28 fractions to the tumor volume and involved lymph nodes.2 The radiation
oncologist suggested using a volumetric modulated arc therapy (VMAT) technique to deliver the
dose at the time of CT simulation.
Patient Setup/Immobilization: After completing induction chemotherapy, JE underwent CT
simulation on March 11, 2015. The patient was positioned head-first supine with his arms above
his head using an arm shuttle made by Qfix. A Qfix breast board was positioned underneath the
arm shuttle so that a board number could be recorded. In this way, the superior and inferior
setup of the patient could be consistent and reproducible. A vacloc bag was positioned under the
head and upper thorax in order to help with arm support and immobilization. A knee sponge was
positioned under the knees for patient comfort (Figures 1 & 2).
The simulation was completed utilizing a 4D motion management CT and a free-breathing CT.
In this way, the radiation oncologist could use the 4D CT in order to evaluate target motion when
creating a planning target volume (PTV). Both treatment planning and contouring were
completed on the free breathing CT scan. IV and oral contrast were used during the exam to
further assist with tumor localization.
Anatomical Contouring: Following completion of the CT simulation, the treatment planning
CT was imported into the Varian Eclipse treatment planning system to be contoured. As per the
protocol, the physician used the prechemotherapy PET scan in order to delineate a gross tumor
volume (GTV) and clinical target volume (CTV). After assessing tumor motion with the 4D
scan, a proper margin was applied to the CTV to create an internal target volume (ITV) and
PTV, accounting for setup error and motion. In addition to these volumes, the radiation
oncologist also contoured organs at risk such as: small and large bowel, the celiac artery,
duodenum, and stomach. The medical dosimetrist contoured organs at risk such as: the heart,
lungs, spinal cord, kidneys, and liver. In addition to organs at risk, the dosimetrist also
contoured immobilization in the treatment area along with any contrast. The immobilization was
then included into the body contour for dose calculation purposes and the contrast was
overridden to a CT value of 40 for correction.
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Beam Isocenter/Arrangement: Due to the size and length of the PTV that was drawn, it was
apparent that a plan exclusively using a VMAT technique would have difficulty meeting the lung
constraints outlined in the protocol. Due to this reason, the planning dosimetrist decided to
utilize a hybrid plan with half of the prescription delivered using static opposed beams, and the
other half delivered using a VMAT plan.
The overall treatment was planned on a Varian Truebeam SD machine that has 6, 10, and 15 MV
photon energies available. Isocenter was placed close to the rotational center of the PTV
(Figures 3-6). An AP and PA beam arrangement was chosen for the conformal part of the
treatment because this arrangement involved the least amount of lung. A 1 mm block margin
was used for these beams to further limit inclusion of the lungs (Figures 7 and 8). An energy of
15 MV was used due to the tumor being located close to midline and both beams were weighted
evenly.
The VMAT portion of the hybrid plan involved 3 coplanar partial arcs using an energy of 6 MV.
The first arc traveled from a gantry angle of 350 to 178 with a collimator rotation of 5. The
slight turn of the collimator helped to better orient the multileaf collimators (MLCs) so that
normal tissue could be better spared. Arc 2 started at gantry 179 and ended at 351 with a
collimator rotation of 355. Turning the collimator the opposite direction again helped in
blocking, but also aided in reducing the overlap of inter-leaf leakage between arcs. The final arc
traveled from 350 to 178 with a collimator turn of 90. With this arc, the field was focused
down to the most bulky portion of the PTV to further modulate this segment and make the
isodose lines more conformal. The gantry angles of these arcs were chosen so as not to enter
through the unaffected lung and to stay off of the spinal cord (Figure 9).
Treatment Planning: All treatment planning for this case was completed using Varian Eclipse
version 11.0. In order to meet the lung objectives outlined in the CALGB 80803 protocol, a
hybrid plan was used over a VMAT plan mainly to reduce the dose delivered to a large volume
of healthy lung. Various studies have shown that treating high volumes of lung to low doses
such as 5, 10, and 13 Gy can greatly increase the risk of radiation pneumonitis and treatment
related complications.3 The results from a retrospective study completed by Mayo et al3 showed
that the use of hybrid IMRT planning in esophageal cancer reduced the volumes of lung
receiving 5, 10 and 20 Gy by 16%, 20%, and 7% respectively when compared to a 9 field IMRT
plan.
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The conformal portion of the hybrid plan was created first and the daily tumor dose was halved
in order to plan using 90 cGy per fraction for 28 fractions. This arrangement was used to avoid
as much lung as possible but also to help control the low to intermediate dose spillage after
delivery of the VMAT plan. Depending on the scenario, more than half of the prescription dose
may be delivered using an AP/PA field arrangement as long as spinal cord dose is under
tolerance.3 The VMAT portion of the plan was then created using the AP/PA portion as a base
dose plan. Utilizing a VMAT technique helped to increase the conformity of the high dose in
order to best treat the PTV. This provided the IMRT-tightness of the VMAT plan while keeping
half of the dose central and out of the lungs. Each plan was normalized so that 95% of the PTV
on the plan sum was receiving 100% of the prescription dose (Figure 10-12).
Unfortunately, due to the size and location of the PTV not all of the suggested objectives for
organs at risk could be met as outlined in CALGB 80803. However, the hybrid plan did meet all
of the required constraints for the patient to remain on protocol (Figure 13). For example, the
objectives for the lungs stated that the volume of lung receiving 20 Gy (V20) must not exceed
30% and the volume of lung receiving 10 Gy (V10) must not exceed 50%. The plan was able to
achieve a V20 of 16.3% and a V10 of 45.9%. The spinal cord had a maximum constraint (0.03 cc)
of 45 Gy and the max dose for the patient was recorded as 43.17 Gy. Finally, the protocol stated
that the mean dose for the heart needed to be less than 30 Gy and a mean dose of 29 Gy was
achieved with the hybrid plan (Figure 14).2
Quality Assurance/Physics Check: Our department uses RadCalc as an independent check of
the monitor units calculated by the treatment planning system. Each plan was copied into a
quality assurance course and a calculation point was inserted specifically for RadCalc. The
monitor units for both plans were calculated within 3% difference, a department standard. In
addition, the VMAT portion of the plan had to be scheduled for portal dosimetry on the linear
accelerator. For this, the electronic portal imaging device (EPID) of the machine is pulled out
and the plan is delivered with the couch out of the beam path. The EPID contains an amorphous
silicon diode array and creates a beam fluence as the plan is delivered. The measured results
were then compared to the calculated fluence of the treatment planning system and the plan
passed gamma analysis. Both the monitor unit second check and the IMRT QA were approved
by a physicist before treatment could be delivered.
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Conclusion: A hybrid treatment planning technique blends together the benefits of conformal
and IMRT planning. In this case study, the patient presented with a large PTV, making it
difficult to meet the objectives to organs at risk such as the heart and lungs. With conformal
planning, dose constraints to the heart and the lungs were unable to meet the objectives of the
protocol. Utilizing VMAT as the sole technique made the volume of lung receiving low doses
unacceptable. Combining the two planning techniques made it possible to keep the low dose
within the midline of the patient while keeping the high dose tightly wrapped around the PTV.
This case study helped me to realize that using a hybrid technique can be very beneficial when
the PTV extends along a large portion of the lung and is located medially within the patient. In
this scenario we can deliver a large portion of the dose using an AP/PA beam arrangement and
the other portion using IMRT to help meet normal tissue objectives. In addition to this, I also
learned that VMAT or IMRT planning may not always be the best option depending on the
location of the tumor. Utilizing IMRT helps to achieve a conformal dose distribution at the cost
of a higher integral dose. When a tumor is located within the thorax, the increase in the volume
of normal tissue receiving low dose becomes a problem for the patient.
In contrast to this, there were some concepts that I had difficulty in understanding as I delved
into greater detail. First, some of the greater intricacies of the VMAT portion of the plan were
somewhat harder to comprehend. I have not had exposure to IMRT planning yet, so Im sure I
will grasp these principles as I gain more experience. Secondly, the patient was on a protocol
examining the difference in chemotherapy regimens on treatment outcomes. Chemotherapy
drugs are another topic that I have had little experience to, thus, explaining this portion was
difficult.
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References

1. Bussman L. Digestive System. In Washington CM, Leaver D, eds. Principles and Practice of
Radiation Therapy. St. Louis, MO: Mosby, Inc; 2004: 743-778.

2. Goodman K, Bekaii-Saab T, Ilson D, et al. Randomized Phase II Trial of PET Scan-Directed

Combined Modality Therapy in Esophageal Cancer. Cancer and Leukemia Group B
(CALGB). https://cris.osumc.edu/CCCSR/Webster/DocumentViewer.aspx?docid=60161.
Updated July 2016. Accessed April 4, 2017.

3. Mayo CS, Urie MM, Fitzgerald TJ, Ding L, Lo YC, Bogdanov M. Hybrid IMRT for treatment
of cancers of the lung and esophagus. Int J Radiat Oncol Biol Phys. 2008;71(5):1408-18.
http:// doi:10.1016/j.ijrobp.2007.12.008.
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Figures

Figure 1. Full body image showing patient positioning on Qfix breast board and arm shuttle.
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Figure 2. Superior view showing patients arm position in vacloc bag.

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AP DRR Left Lateral DRR

Figure 3. Digitally reconstructed radiographs (DRRs) indicating isocenter placement.

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Figure 4. Isocenter placement in the axial plane.

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Figure 5. Isocenter placement in the coronal view.

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Figure 6. Isocenter placement in the sagittal plane.

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Figure 7. AP treatment field of the conformal portion of the hybrid plan with a 1 mm MLC
margin to the PTV (red).

Figure 8. PA treatment field with 1 mm MLC margin to the PTV (red).

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Figure 9. Axial view with VMAT arcs turned on showing the start and stop gantry angles of
each of the 3 arcs.
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Figure 10. Isodose distribution of hybrid treatment plan with 100% prescription dose (yellow)
covering 95% of the PTV (inner red). Note the 50% isodose line (bold red) being located
medially.
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Figure 11. Hybrid plan dose distribution in coronal plane with the higher isodose lines
conformal to the PTV (inner red).
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Figure 12. Hybrid plan dose distribution in sagittal plane.

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Figure 13. Planning objectives from CALGB 80803. Objectives in red are requested and
objectives in blue must be met.
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Figure 14. A Dose Volume Histogram (DVH) of the hybrid plan demonstrated the ability to
achieve prescription dose to the PTV (red) while keeping dose to organs at risk lower than
with other treatment techniques.