Chapter 24.
HODGKIN’S DISEASE
CASE STUDY
BILLY W. LOO JR, MD, PHD, RICHARD T. HOPPE, MD, FACR
Patient History
An 8-year-old boy with no significant past medical histo-
ry presented with fevers to 39°C, fatigue, and abdominal
pain with a palpable abdominal mass. Abdominal ultra-
sonography revealed multiple large para-aortic masses. A
computed tomography (CT) scan of the neck, chest,
abdomen, and pelvis revealed a left supraclavicular mass,
massive retroperitoneal lymphadenopathy extending from
the diaphragmatic hiatus to the pelvis, and mesenteric lym-
phadenopathy. The thorax was unremarkable. An exci-
sional biopsy of the left supraclavicular lymph nodes
revealed nodular sclerosing Hodgkin’s disease (CD15 and
CD30 positive, CD20 equivocal). The pathologic diagno-
sis was confirmed by expert review. Bone marrow biopsy
and cytogenetics were normal. Lymphangiography revealed
abnormally enlarged lymph nodes in the iliac and para-
aortic areas. 18F-labeled fluorodeoxyglucose (18FDG)
positron emission tomography (18FDG-PET) revealed glu-
cose hypermetabolism in the left supraclavicular, para-
aortic, and left iliac areas. Laboratory studies at the time
of diagnosis included white blood cell count of 7,800 per
microliter, lymphocyte count of 1,500 per microliter, hemo-
globin of 8.1 grams/deciliter, albumin of 3.7 grams/deciliter,
and an erythrocyte sedimentation rate of 73 millime-
ters/hour.
The patient was assigned an Ann Arbor stage of IIIB
and was enrolled in the unfavorable-risk arm of the St.
Jude Children’s Research Hospital risk-adapted therapy
protocol for pediatric Hodgkin’s disease (HOD99), with
treatment consisting of three cycles of alternating
VAMP/COP (VAMP = vinblastine, doxorubicin, methotrex-
ate, prednisone; COP = cyclophosphamide, vincristine,
procarbazine) chemotherapy followed by involved field
radiation therapy (RT). Restaging studies were obtained
per protocol following one cycle of VAMP/COP. CT revealed
a complete response in the left supraclavicular area and a
marked but partial response in the para-aortic and pelvic
547
areas with significant residual bulk. 18FDG-PET demon-
strated no residual areas of hypermetabolism. According
to protocol, he was to receive 15 Gy to the left supraclav-
icular area and 25.5 Gy to the spleen, para-aortic, and iliac
areas in 1.5 Gy daily fractions following the completion of
chemotherapy.
He was treated with conventional CT-planned RT. An
attempt was made to use a shrinking field technique to
achieve maximal sparing of the kidneys given their close
proximity to the bulk of the disease. He received 15 Gy to
the supraclavicular field and 16.5 Gy to the infradi-
aphragmatic field delivered using opposed anterior-
posterior ports. A repeat treatment planning CT scan
revealed no significant reduction in tumor volume, and an
additional 9 Gy was delivered to the inferior field via slight-
ly oblique opposed portals. Significant underdosing of por-
tions of the tumor mass was accepted to restrict the dose
to the kidneys. His treatment course was complicated by
nausea and vomiting, which were adequately managed with
conservative measures. We present here the conventional
plan compared with a hypothetical intensity-modulated
radiation therapy (IMRT) plan that demonstrates some
dosimetric advantages.
Simulation
The patient was positioned in the supine position, with
arms in a slight akimbo position. A custom binary foam
anatomic mold (Alpha Cradle, Smithers Medical Products,
Inc., Hudson, OH), extending from above the head to the
level of the buttocks, was used for immobilization. Custom
handholds for reproducing the position of the upper extrem-
ities were integrated into the mold. CT simulation was per-
formed using an AcQSim PQ5000 scanner (Philips Medical
Systems, Andover, MA). CT slices from the base of the skull
to the upper thighs were acquired with 4 mm spacing.
Intravenous contrast was not used. The same procedure
was repeated for planning the cone-down treatment.
548 / Intensity-Modulated Radiation Therapy

Target and Tissue Delineation
All target and normal tissue segmentation was performed
manually using an AcQSim VoxelQ workstation (Philips
Medical Systems). In the abdomen, the grossly involved
nodal mass was contoured as the gross tumor volume
(GTV). To define the clinical target volume (CTV), a uni-
form 1 cm expansion was created around the GTV. This
volume was modified to prevent expansion into adjacent
normal structures; expansion into surrounding fat and
muscle was allowed. Consequently, in the vicinity of the
kidneys, where the GTV abutted the critical structures,
there was little to no expansion. The spleen and remainder
of the para-aortic and common iliac nodal chains were
included as contiguous sites of potential microscopic dis-
ease. Because unenlarged lymphatic structures cannot be
visualized reliably by CT, we used the corresponding vas-
cular structures (ie, aorta, inferior vena cava, and iliac ves-
sels) as surrogate anatomic landmarks. In this case, the
presence of residual contrast from the previous lymphan-
giogram also aided target definition. The following nor-
mal tissues were delineated and included in the IMRT
optimization process: left and right lungs, left and right
kidneys, liver, stomach, bowel, spinal cord (contoured from
the T8 to L3 levels), and vertebrae (T8 to S3). Representative
slices from the treatment planning CT scan are shown in
Figure 24.1-1.
Treatment Planning
For the conventional treatment plan, an internal margin
for organ motion (eg, from breathing) was not considered
for most structures of interest. However, for quality assur-
ance, we perform an additional fluoroscopic simulation
with blocks in place prior to treatment. At that time, we
also verify that there is an adequate margin on the left
hemidiaphragm at natural end-expiration to ensure cov-
erage of the spleen superiorly throughout the respiratory
cycle. In this case, there was essentially no planning target
volume (PTV) expansion in the vicinity of the kidneys, and
the block edges projected very close to the edges of the seg-
mented GTV. This can be seen in Figure 24.1-2, the ante-
rior port of the conventional treatment field.
Given the presumably greater sensitivity of IMRT treat-
ments to organ motion, basing the PTV expansion on a
measurement of organ motion would be desirable. This
could be accomplished by acquiring CT scans at natural
end-inspiration and end-expiration. In the case presented

FIGURE 24.1-1. Sections from the treatment planning computed tomography scan, with targets
and anatomic structures segmented. CTV = clinical target volume; GTV = gross tumor volume. (To
view a color version of this image, please refer to the CD-ROM.)
 Hodgkin’s Disease: Case Study / 549

We used CORVUS, version 4.0 (North American

Scientific, NOMOS Radiation Oncology Division,
Cranberry Township, PA), IMRT treatment planning soft-
ware. The input parameters described here are specific to
this software package, and are shown in Table 24.1-1. Tissue
heterogeneity correction was used for both optimization
and dose calculation. To demonstrate the general applica-
bility of IMRT, an attempt to fine-tune the choices of input
parameters (other than to emphasize kidney sparing in the
dose specification) was not made.
For the IMRT plan, we chose five coplanar beams with
uniformly spaced beam angles at 36, 108, 180, 252, and 324
degrees (where 180 degrees corresponds to an anterior-
posterior beam). At three of the above beam angles, the
treatment field was divided in two by the CORVUS plan-
ning system because the field width is limited by the max-
imum travel of the Varian multileaf collimator (Varian
Medical Systems, Palo Alto, CA) leaves in dynamic delivery
mode. Thus, there were 8 fields and 808 field segments.
We chose a beam energy of 6 MV (same as in the conven-
FIGURE 24.1-2. Anterior port of the conventional spade field. CTV =
tional plan) to enable a more direct comparison. A signifi-
clinical target volume; GTV = gross tumor volume. (To view a color ver-
cant improvement in dose conformity can be achieved by
sion of this image, please refer to the CD-ROM.)
using a larger number of beam angles (eg, seven to nine;
not shown) or by optimizing the choice of beam angles.2 A
smaller improvement can be achieved by using higher beam
energy (eg, 15 MV; not shown) at the potential cost of a
higher total-body effective dose from photoneutrons pro-
here, the initial and subsequent cone-down planning scans
duced in the head of the linear accelerator. Of note, we often
were performed without controlling for breathing.
deliver IMRT treatments employing up to 15 or more fields
However, the initial scan was acquired in relative expira-
in our clinic with total treatment times (including patient
tion, whereas the cone-down scan was acquired in relative
positioning and treatment delivery) of approximately 30 to
inspiration, providing a retrospective estimate of organ
40 minutes.
motion. The two scans were fused using bony anatomy,
and the corresponding structures were contoured on both
scans. This revealed that with respect to the targets, the TABLE 24.1-1. Input Parameters
spleen was the most mobile and on inspiration moved infe- Volume
riorly and posteromedially, with a maximum displacement Goal, below Minimum, Maximum, Target
of approximately 2 cm superior-inferior, 2.3 cm left-right, Target Gy Goal, % Gy Gy Type
and 1.2 cm anterior-posterior; the superior part of the GTV 25.5 5 20 27 Homogeneous
GTV had approximately 0.4 cm superior-inferior and min- CTV 25.5 5 20 27 Homogeneous
imal anterior-posterior and left-right excursions; the Spleen 25.5 5 20 27 Homogeneous
remainder of the CTV and GTV was relatively station- Volume
ary. Among nontarget tissues, the liver had approximate- Limit, above Minimum, Maximum, Structure
ly 2 cm superior-inferior and 1.5 cm left-right excursions; Structure Gy Limit, % Gy Gy Type
the kidneys had approximately 0.6 cm superior-inferior R kidney 8.0 10 3 20 Critical
and minimal anterior-posterior and left-right excursions. L kidney 8.0 10 3 20 Critical
These measurements are consistent with published data Spinal cord 15.0 10 5 20 Basic
on organ motion and were used for defining the internal Vertebrae 15.0 10 5 20 Basic
Bowel 15.0 20 5 20 Basic
margin parameters.1 It is important to note, however, that
Stomach 15.0 20 5 25 Basic
unlike for static conventional fields, accounting for organ Liver 15.0 20 5 25 Basic
motion simply by PTV expansion may be inadequate for R lung 15.0 20 5 25 Basic
IMRT, which is a dynamic delivery modality. We are cur- L lung 15.0 20 5 25 Basic
rently implementing respiratory cycle gating of planning CTV = clinical target volume; GTV = gross tumor volume; R = right; L = left.
scans and treatment delivery and investigating other meth- These parameters and their definitions are specific to the CORVUS 4.0 treatment
ods of breathing adapted treatment as well. planning system.
550 / Intensity-Modulated Radiation Therapy

Dose-volume histograms of target structures and nor-
mal tissues comparing the conventional plan with the IMRT
plan are shown in Figures 24.1-3 to 24.1-6. The corre-
sponding isodose curves for selected slices are shown in
Figure 24.1-7. These demonstrate that compared with the
conventional treatment plan, IMRT results in improved
target coverage and kidney sparing simultaneously. In prin-
ciple, this should result in improved probability of dis-
ease control and decreased risk of late kidney dysfunction.
In addition, there is better exclusion of the spinal cord, ver-
tebrae, stomach, bowel, and liver from the high-dose regions.
The reduction in normal tissue irradiated may decrease
short-term toxicities such as nausea, diarrhea, and marrow
suppression; intermediate-term symptoms such as
L’hermitte’s sign; and late complications such as bowel
obstruction. Whether such improved clinical end points
are realized remains to be borne out by clinical studies.
Treatment Delivery and Quality
Assurance
The conventional treatment consisted of five fields (anteri-
or, posterior open, posterior with wedge, right anterior
oblique, left posterior oblique), requiring 2,989 monitor

100
100
90
90
80 GTV
CTV 80
Cumulative Frequency

70 Spleen
Cumulative Frequency
70
60 R Kidney
L Kidney 60
50 Spinal Cord
Conv 50
40 IMRT Vertebrae
40 Conv
30 IMRT
30
20
20
10
10
0
0 5 10 15 20 25 30 35 0
Dose (Gy) 0 5 10 15 20 25 30 35
Dose (Gy)

FIGURE 24.1-3. Dose-volume histograms of conventional versus inten- FIGURE 24.1-4. Intensity-modulated radiation therapy (IMRT) results
sity-modulated radiation therapy (IMRT) treatment plans. IMRT results in substantially lower doses to the spinal cord and vertebrae. (To view
in both improved target coverage and kidney sparing. (To view a color a color version of this image, please refer to the CD-ROM.)
version of this image, please refer to the CD-ROM.)

14
100
Stomach
12
Cumulative Irradiated Volume (L)

90 Bowel
80 Liver
Conv 10
Cumulative Frequency

70 IMRT Nontarget Tissue

60 8 Conv
IMRT
50
6
40
30 4

20
2
10

0 0
0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35
Dose (Gy) Dose (Gy)

FIGURE 24.1-5. With intensity-modulated radiation therapy (IMRT), a FIGURE 24.1-6. Intensity-modulated radiation therapy (IMRT) results in
smaller volume of abdominal organs receives higher doses (above a reduction in the volume of all nontarget tissues receiving higher doses
10–17 Gy), whereas a larger volume receives lower doses. (To view a (> 10 Gy) at the cost of an increase in the volume receiving lower doses.
color version of this image, please refer to the CD-ROM.) (To view a color version of this image, please refer to the CD-ROM.)
 Hodgkin’s Disease: Case Study / 551

FIGURE 24.1-7. Isodose curves of conventional versus intensity-modulated radiation therapy (IMRT) treatment plans demonstrate improved dose
conformity with IMRT. (To view a color version of this image, please refer to the CD-ROM.)

units over the entire treatment course to deliver 25.5 Gy to
the reference point in the target. The IMRT treatment plan
above would comprise eight fields (five beam angles, with
three fields split in two, as described above), with 808 seg-
ments requiring 17,425 monitor units over the treatment
course to deliver 25.5 Gy to the 69.5% isodose line, which
encompasses 90% of the GTV. The 5.8 times greater num-
ber of monitor units required by IMRT in this case would
result in similarly increased leakage radiation from the head
of the linear accelerator, contributing to a higher total-body
dose. On the other hand, the total-body dose from internal
scatter from the irradiated tissues is slightly lower with IMRT
owing to the smaller volume of tissue receiving the high-
est doses. Within the irradiated field, IMRT results in a small-
er volume of nontarget tissues receiving higher doses (above
10 Gy) at the cost of a larger volume receiving lower doses
(see Figure 24.1-6). However, there are insufficient data to
predict whether these dosimetric results would result in a
greater or lesser risk of radiation-induced secondary malig-
nancies with IMRT compared with conventional RT, and
552 / Intensity-Modulated Radiation Therapy
well-designed clinical trials are needed to evaluate this impor-
tant question in this highly curable patient population.
Of note, improvements in IMRT planning and delivery
have the potential to greatly improve its efficiency and
decrease the excess radiation to nontarget tissues.
Optimizing the choice of beam angles may result in
improved dose conformity. Additionally, fewer beam angles
may achieve the same degree of conformity, which could
result in a smaller volume of tissue irradiated even to lower
doses.2 Direct optimization of the beam apertures as
opposed to the beamlet intensities can reduce the treat-
ment complexity and thereby the required number of mon-
itor units substantially (potentially by over 70%) without
compromising dose conformity.3,4 Both of these improve-
ments could significantly reduce the total-body doses from
IMRT without diminishing its dosimetric advantages over
conventional treatment.
Clinical Outcome
At nearly 2 years follow-up after completing treatment with
conventional RT, the patient had no clinical or radiographic
evidence of disease recurrence and no symptoms referable
to late treatment-related toxicity.
Our dosimetric planning study of IMRT in Hodgkin’s
disease was presented earlier.5 In that review, convention-
al and IMRT planning was compared in three patients (two
adults with bulky mediastinal disease and a child with bulky
para-aortic disease). Compared to conventional planning,
treating the periphery of the GTV using IMRT resulted in
an effective dose escalation to most of the GTV due to the
inherent heterogeneity of GTV coverage with IMRT.
Coverage of the CTV was improved, particularly in the
supraclavicular region. As shown above in the case of bulky
para-aortic disease, IMRT planning resulted in better GTV
coverage as well as sparing of the kidneys.
References
1. Langen KM, Jones DT. Organ motion and its management. Int
J Radiat Oncol Biol Phys 2001;50:265–78.
2. Pugachev A, Xing L. Pseudo beam’s-eye-view as applied to
beam orientation selection in intensity-modulated radiation
therapy. Int J Radiat Oncol Biol Phys 2001;51:1361–70.
3. Shepard DM, Earl MA, Li XA, et al. Direct aper ture
optimization: a turnkey solution for step-and-shoot
IMRT. Med Phys 2002;29:1007–18.
4. Cotrutz C, Xing L. Segment-based dose optimization using a
genetic algorithm. Phys Med Biol 2003;48:2987–98.
5. Loo BW Jr, Crooks SM, Xing L, et al. A dosimetric comparison
of conventional and intensity modulated radiation therapies
for the treatment of Hodgkin’s disease. Int J Radiat Oncol
Biol Phys 2002;54(suppl 2):323.