Chapter 26.
NEUROBLASTOMA
CASE STUDY
ROBERT S. LAVEY, MD, MPH, ARTHUR J. OLCH, PHD
Patient History
A 4-year-old boy presented with a 1-month history of pro-
gressive fatigue, anorexia, weight loss, pallor, and inter-
mittent abdominal pain. A computed tomography (CT)
scan demonstrated a 10 × 9 × 9 cm heterogeneous, mod-
erately enhancing, lobulated retroperitoneal mass encas-
ing the aorta and inferior vena cava and extending from
the level of the T9 to the L5 vertebral body. A 1 × 1 × 3 cm
left paraspinous mass was also noted at the level of the
T4 and T5 vertebral bodies, consistent with neuroblas-
toma. Laboratory tests revealed significant anemia and ele-
vated serum homovanillic acid and vanillylmandelic acid
levels. Metastatic workup included a bone scan and 123I-
metaiodobenzylguanidine (MIBG) scan, both of which
showed widely disseminated bone metastases. Bone mar-
row biopsy confirmed the diagnosis of neuroblastoma.
The patient was enrolled in the Children’s Oncology
Group (COG) protocol A3973 for high-risk neuroblas-
toma and received six cycles of induction chemotherapy,
including cyclophosphamide, doxorubicin, and vincristine
in cycles 1, 2, 4, and 6 and cisplatin and etoposide in cycles
3 and 5. A repeat CT scan following the fourth cycle of
chemotherapy showed resolution of the left paraspinous
mass and a decrease in size of the retroperitoneal mass to
4 × 4 × 6 cm with calcific areas.
The abdominal tumor was subtotally resected following
the fifth cycle of chemotherapy, with residual unresectable
disease in the porta hepatis. A postoperative CT scan showed
a residual tumor mass 3.5 × 3 × 2 cm in the porta hepatis
region. Repeat 123I-MIBG scanning demonstrated resolu-
tion of all metastatic sites but persistence of increased uptake
in the right upper quadrant. Following consolidation mye-
loablative chemotherapy (melphalan, etoposide, and car-
boplatin) with autologous stem cell rescue, the patient was
referred for radiation therapy (RT) of the preoperative
retroperitoneal tumor volume per the guidelines of the COG
high-risk neuroblastoma protocol. In an effort to spare the
surrounding normal tissues, intensity-modulated radiation
therapy (IMRT) was used in this patient.
584
Simulation
The patient was sedated during simulation (and daily RT)
using intravenous continuous-infusion propofol because
of his young age. His trunk and lower extremities were
positioned in the BodyFix cushion, a custom-molded, bead-
filled, evacuated vinyl bag (Medical Intelligence,
Schwabmünchen, Germany) shown in Figure 26.2-1. Marks
were drawn on the patient and the bag for reproducibili-
ty of positioning. A planning CT scan (Lightspeed QX/I,
GE Medical Systems, Waukasha, WI) of the abdomen was
obtained with the patient in the BodyFix using a slice sep-
aration and thickness of 2.5 mm.
Target and Tissue Delineation
The gross tumor volume (GTV) consisted of the primary
tumor volume (visualized on the CT scan done between the
fourth cycle of chemotherapy and partial resection). The plan-
ning target volume (PTV) consisted of the GTV plus a 5 mm
margin. Organs at risk (OAR) delineated in this patient includ-
ed the kidneys, liver, and vertebral bodies. The GTV and OAR
were contoured manually on each axial CT slice. The PTV
was generated from the GTV by the treatment planning soft-
ware and was altered manually to give a 2 mm rather than a
5 mm margin on the kidneys and vertebral bodies. A three-
dimensional reconstruction of the GTV and PTV is shown
in Figure 26.2-2A and outlines of the PTV in the sagittal, axial,
and coronal planes are given in Figure 26.2-2B–D.
Treatment Planning
The IMRT plan was generated using the Plato Inverse
Treatment Planning software, version 1.1, and Plato Radiation
Treatment Planning System software, version 2.6, modules
(Nucletron BV, Veenendaal, the Netherlands). The input
parameters for the PTV were weighted maximum and min-
imum doses. The liver and nonspecified tissues (body) had
input parameters that were weighted maximum doses (Tables
26.2-1 and 26.2-2). For the kidneys and vertebrae, desired

FIGURE 26.2-1. (A) The custom-molded BodyFix positioning and immobilization device made for the patient in this case study. (B) The patient secured
in his BodyFix on the computed tomography scan platform with the target localizer box mounted for positioning the couch. The target localizer box
was removed prior to treatment daily. (To view a color version of this image, please refer to the CD-ROM.)
dose-volume histograms were constructed by inputting six
dose-volume points into the planning software. The PTV
was planned to receive a cumulative dose of 2,160 cGy given
in 12 equal daily fractions of 180 cGy.
Eight coplanar beams, all with a couch angle of 180°,
were selected to deliver the IMRT plan. The beam angles
were chosen to avoid the passage of any entry beam through
the couch rails. The gantry angles for beam delivery were
35, 85, 125, 165, 200, 240, 275, and 325 degrees. The beams
were 16.5 to 17.0 cm long at 100 cm source-axis distance.
One hundred seventeen beam segments were used. The
beamlets were 5 × 5 mm. The photon energy of each beam
was 6 MV. The resultant isodose distributions overlaid on
sagittal, axial, and coronal CT slices are shown in Figure
26.2-2. The final plan gave a minimum of 100% of the pre-
scribed dose to 95% of the PTV. The dose-volume his-
tograms of the PTV and OAR are shown in Figure 26.2-3.
Treatment Delivery and Quality
Assurance
The dose calculations from the Plato treatment planning
software were verified by both ionization chamber and film
measurements prior to delivery of the first treatment. The
IMRT plan was applied to a 30 × 30 × 10 cm phantom with
the isocenter in the center of the phantom. The ioniza-
tion chamber air volume (0.6 cc chamber) was contoured
into the center of the phantom, permitting calculation of
the mean dose in the air volume. The three-dimensional
dose grid was calculated by the Plato treatment planning
software and stored as a single file. The file was transferred
to RIT (Radiological Imaging Technology, Colorado Springs,
CO) film dosimetry software to permit extraction of iso-
doses in a coronal plane 1 cm anterior to the isocenter.
Neuroblastoma: Case Study / 585
The plan was transferred to a Varian linear accelerator
(Varian Medical Systems, Palo Alto, CA), and a 30 × 30 ×
10 cm solid water phantom was positioned on the treat-
ment couch such that the center of the phantom was at the
gantry isocenter. A 0.6 cc ionization chamber was placed
in the center of the phantom, and a film (EDR2, Eastman
Kodak, Rochester, NY) was placed in the same coronal plane
as was calculated by the treatment planning software. The
phantom (with chamber and film) was given a mock IMRT
treatment, delivering the exact beams and monitor of units
of the patient’s plan. The charge recorded by the elec-
trometer was converted into dose and compared with that
calculated by the planning system. The allowed difference
was 3%. A calibration film was processed along with the
EDR2 film. Both films were scanned by a Vidar 16-bit
Dosimetry Pro scanner (Vidar Systems Corporation,
Herndon, VA), and scanner units were converted to dose
using the calibration film. The EDR2 film and the Plato
coronal plane dose patterns were then registered and dig-
itally overlaid using the RIT software. Visual and analytic
comparisons were made for doses above 20% of the isocen-
ter dose. The tolerance for agreement in the high dose gra-
dient areas was 3 mm and in the high dose/low gradient
areas was 3%.
In addition to dual verification of the dose calculations,
multiple system-wide quality assurance tests were con-
ducted. The performance of the multileaf collimator was
checked daily by measuring the dose delivered to the cen-
tral channel of a Keithley Tracker (Keithley Instruments,
Inc, Cleveland, OH) irradiated by a standard dynamic plan.
A film consisting of a composite of two complex patterns,
the first of which is the negative of the second, was taken
once weekly. The appropriate result is a series of uniform-
ly dark bars separated by unexposed bars. If any result was
586 / Intensity-Modulated Radiation Therapy

FIGURE 26.2-2. (A) Three-dimensional reconstruction of the child’s abdomen, showing the gross tumor volume in blue, planning target volume
(PTV) in red, vertebral bodies in purple, kidneys in green, liver in yellow, and entry directions of the eight treatment beams. (B) to (D) Computed tomog-
raphy (CT) slices (B) sagittal; (C) axial; (D) coronal) showing isodose distribution in the abdomen. The PTV is outlined in red, the 180 cGy isodose line
(corresponding to a cumulative dose of 2,160 cGy) is green, the 125 cGy isodose line (corresponding to a cumulative dose of 1,500 cGy) is green, and
the 84 cGy isodose line (corresponding to a cumulative dose of 1,000 cGy) is blue. (To view a color version of this image, please refer to the CD-ROM.)

TABLE 26.2-1. Input Parameters: Specified Doses and TABLE 26.2-2. Input Parameters: Weighting and Dose-Volume
Weighting for the Planning Target Volume, Body, and Liver* Points for the Kidneys and Vertebral Bodies
Maximum Weight, Minimum Organ Weight, % Gy/%V Gy/%V Gy/%V Gy/%V Gy/%V Gy/%V
Organ Dose, Gy % Dose, Gy Weight, %
Kidneys 80 4/100 5/75 11/27 15/14 19/3 20/0
Planning target volume 22 50 21.6 100 Vertebrae 20 3/100 8/34 10/14 17/10 20/7 23/0
Body 15 25 — —
%V indicates the maximum percent volume of the organ at risk that is permit-
Liver 15 50 — —
ted to receive the specified dose.
*All tissues inside the skin surface that were not contoured as gross tumor vol-
ume, planning target volume, or an organ at risk.
 Neuroblastoma: Case Study / 587

found to be outside tolerance limits, the error would be

located and corrected.
Treatment was delivered on a Varian 2100C linear accel-
erator equipped with the integrated Millennium 120-leaf
collimator (Varian Medical Systems) in the “step-and-shoot”
mode. Orthogonal anterior-posterior and left lateral digi-
tal images of the treated region were taken on the first day
of treatment and at least once weekly throughout the treat-
ment course. These images were compared with digitally
reconstructed radiographs of the same projections made
from the treatment planning CT scan. The field position
was adjusted if there was a 2 mm or greater disparity in the
anterior-posterior, superior-inferior, or medial-lateral direc-
tion between the digital Portal Vision (Varian Medical
Systems) images and the digitally reconstructed radiographs.

Clinical Outcome
The patient tolerated IMRT well, without experiencing nau-
sea or fatigue. He has been taking 13-cis–retinoic acid oral-
FIGURE 26.2-3. Cumulative dose-volume histogram of the planning tar-
ly as maintenance therapy per protocol guidelines since the
get volume (PTV) and the specified organ at risk (liver, kidneys, and ver-
completion of IMRT. Body CT and 123I-MIBG scans
tebral bodies).
obtained at 4 months following IMRT showed no evidence
of residual or recurrent disease. He was last examined at
age 5.5 years, 6 months following completion of IMRT.
At that time, he remained asymptomatic with normal diet,
behavior, and physical activity.