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Phillip Lin

DOS 711 Research Methodology Med Dos I

4/9/17

Hippocampal-Sparing WBRT

History of Present Illness: Patient DB is a 58-year-old male with now stage IV

melanoma and presented with symptomatic brain metastases. He had a history of stage II
melanoma on his lower back status-post resection and underwent a bilateral sentinel
lymph node biopsy (which was negative) back in August 2000. He received no adjuvant
therapy at the time and was in a normal state of health. He then presented on 9/15/16 with
1-2 weeks of symptoms including fever, nausea, emesis, dizziness, balance difficulty,
photosensitivity, headaches, and difficulty focusing at work. He was admitted to the
intensive care unit (ICU) and underwent magnetic resonance imaging (MRI) of the brain
on 9/15/16. A left sub-occipital craniotomy and tumor resection was performed the next
day.

On 9/26/16, the patient presented to the hospital again with 1-2 days of left facial droop
and left handed weakness. A computed tomography (CT) scan of the head was performed
that day and then posterior and anterior decompression surgeries were performed the next
day resulting in a significant improvement in symptoms.

The patient presented again on 10/17/16 to the emergency department (ED) with dimmed
and narrowed field of vision, fatigue, and disorientation. He was discharged with
Decadron which was increased from 2 mg two times a day (BID) to 2 mg three times a
day (TID). An MRI of the brain was performed the same day.

Two days after his admittance to the ED, the patient was referred to radiation oncology
and reports overall feeling quite well. He still feels disoriented, moving slowly through
everyday tasks, and has difficulty with balance while walking and reporting tunnel
vision. However, he does not report blurry or double vision and he and his wife state
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that there are short-term memory problems but his strength is near baseline. The patient
has a normal appetite with no significant weight loss. His bowel and bladder function are
reported as normal.

Past Medical History:

DB is fairly healthy and has minimal past medical history. A lumbar spine surgery was
performed in 1998 and he denies past radiation therapy and chemotherapy treatment. He
has no known allergies.

Social History: DB is married with two children. He works as a federal judge and has no
history or tobacco or drug use. He drinks alcohol rarely and denies drug use. When asked
about a family history of malignancies, he reports none.

Medications: DBs only reports taking melatonin to help him sleep occasionally.
Medications associated with his symptomatic brain metastases include dexamethasone
(DECADRON) to reduce cerebral edema, and levetiracetam (KEPPRA) for prevention of
seizures.

Diagnostic Imaging:

On 9/15/16, an MRI of the brain displayed a total of at least 9 intracranial lesions with the
largest measuring 4 x 3 x 2.3 cm within the posterior cerebellum and second largest in the
right frontal lobe with a maximum diameter of 3.7 cm. A CT scan of the head on 9/26/16
showed an increasing right frontal hemorrhagic lesion with the other lesions slightly
increased in size. On 10/17/2016, an MRI of the brain without contrast demonstrated
increasement in size and number of metastases, recurrence of the recently resected
disease, and ependymal seeding. Additional MRIs were needed for treatment planning
and ordered at time of consult which included a gadolinium contrast enhanced T1-
weighted MRI, high definition 3D spoiled gradient MRI, and a T2 Flair MRI. These were
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all acquired in 1.25mm slices to coincide with the radiation oncology CT planning slice
thickness and accuracy of imaging fusion registration.

Radiation Oncologist Recommendations:

Radiotherapy options provided to the patient included whole brain radiation (WBRT)
alone, whole brain radiation with a stereotactic radiosurgery (SRS) boost, or SRS alone.
The patient was informed of the potential short and long-term side effects of each option
and understood that the intent is palliative and not curative given that he has metastatic
disease. Given his numerous symptomatic lesions with evidence of rapid progression
from the most recent MRI, the radiation oncologist recommended that whole brain
radiation would be the standard of care of radiotherapy. A discussion was performed with
other oncologists and the option of immunotherapy was offered if he was to defer
radiation therapy. In the case of a favorable response to systemic therapy, SRS to the
large lesions causing neurological symptoms to the patient could be done. Should he
continue to progress on immunotherapy, WBRT can be offered quickly.

The Plan (prescription): After immunotherapy had not shown adequate control in an
MRI obtained 1-month post treatment, the plan for WBRT was offered with a
hippocampal sparing technique in hopes to prevent neurocognitive function deterioration.
A dose of 300 cGy delivered in 10 fractions (consecutively for 5 days a week) resulting in
a total of 3000 cGy to the volume of the whole brain while avoiding the hippocampal
region.

Patient Setup/Immobilization: The patient was positioned head-first, supine with a

head/face aquaplast mask on a Civco S-frame that is indexed on the treatment table. For
treatment, the head mask is positioned on the superior portion to the treatment couch so
that there is no couch attenuation contributing to the posterior beam angles. The head
position was resting in a neutral position on a B cup Silverman headrest to allow for
ease of treatment field setup. See pictures below for patient setup:
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Patient is positioned head-first supine with a head mask indexed on a Civco S-frame
board. A neutral stanced headrest with a custom molded cushion helps to support the
head. A knee roll is placed under his knees for patient comfort while lying on his back.

Anatomical Contouring: Anatomy contoured included the whole brain tissue, bilateral
orbits, bilateral lens, hippocampus, spinal cord, optic nerves, and optic chiasm for dose
calculation and to avoid organs at risk (OR). A hippocampal avoidance region was
generated by creating a 5mm margin structure from the hippocampus contour which took
into account necessary dose fall-off between the hippocampus and whole brain planning
treatment volume (PTV).1 In addition, the lens were a big concern considering their low
tolerance dose and were present within the beams projected path. An avoidance structure
was created around their contours with a 5mm margin. See pictures below:
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The most critical structures have an avoidance margin created around them:
hippocampus contoured (green) with a 5mm avoidance margin (pink) displayed on the
left (axial view). The right and left lens of the eyes had a 5mm avoidance margin
surrounding them as well (pictured right).
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Beam Isocenter/Arrangement: Isocenter was placed in the center of the contoured brain
volume with three 360 degree arcs delivered for each fraction. Treatment was delivered
isocentrically (source-axis distance or SAD technique) with a Varian TrueBeam linear
accelerator. Between the three full arcs, collimator angles were positioned with a 15
degree, 345 degree, and 270 degree rotation to avoid excessive overlap that occurs due to
multileaf collimator (MLC) leakage at the central axis (CAX). Field sizes were
constructed and reviewed through each arcs beams eye view (BEV) path to ensure the
whole brain volume was irradiated. No treatment couch rotations were necessary to
achieve adequate coverage in the plan. See pictures below:

Shown above: Treatment plan parameters including collimator angles, and field sizes,
and monitor units (MU) calculated.

Shown above: AP (left) and Right Lateral (right) DRR views showing isocenter
placement.

Treatment Planning: An inverse planning technique delivered with volumetric

modulated arc therapy (VMAT) was used. 6 MV was the energy of choice so that dose
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coverage at the lateral aspect of the brain isnt lost.2 A choice of 15 MV energy beams
would cause unnecessary neutron contamination due to the higher amount of monitor
units (MUs) needed with a VMAT plan. Target volume constraints were listed as the
volume receiving 30 Gy (V30) to cover >95% of the PTV (whole brain volume). Dose to
100% of the hippocampi was to be <9 Gy with a dose maximum of <16 Gy to a 0.03
cubic centimeter volume.

From left to right, top to bottom: Axial, Sagittal, and Coronal views of treatment plan
and dose distribution at isocenter. The thick blue lines represent the 95% isodose line
which covered 100% of the brain volume per the radiation oncologists prescription.
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Dose-volume Histogram (DVH) displayed above.

Quality Assurance/Physics Check: Portal Dosimetry delivered on the planned treatment

machine was used to verify the fluence fields of the three VMAT arcs. The fluence fields
were compared and checked by a physicist, passing within a <3% difference. Image
guided radiation therapy (IGRT) was utilized with daily kV pair match and a cone beam
CT (CBCT) to account for accurate patient position, particularly the head roll.

Conclusion: Though this was a palliative treatment course, radiation therapy today can
be designed to deliver treatment to reduce side effects and increase quality of life. The
hippocampus is thought to be the center of emotion, memory, and the autonomic nervous
system. This technique was researched by the patient and requested to the radiation
oncologist. On a socioeconomic level, this plan would not be approved by insurance
since it involves a complex plan and billing charge with a technically simple radiation
treatment. The patient was willing to pay out of pocket to receive this radiation treatment.
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I had learned that even with a palliative goal in mind, technology and research continues
to push forward dosimetry planning techniques to achieve greater patient outcomes and
reduce sequelae. There are not many definitive studies today verifying the added effect of
hippocampal sparing WBRT, but this case shows that with thought and practice,
techniques can be utilized and pushed to achieve greater results for radiation therapy in
the future.
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References
1. Gondi V, Tolakanahalli R, Mehta MP, et al. Hippocampal-sparing whole brain
radiotherapy: a how-to technique, utilizing helical tomotherapy and linac-based
intensity modulated radiotherapy. Int. J. Radiat. Oncol. Biol. Phys.
2010;78(4):1244-1252.
2. Bentel GC. Radiation Therapy Planning. 2nd New York, NY: McGraw-Hill; 1996.