1

Diffuse large B-cell lymphoma: a case study

Authors: Adriana Dalea, B.S, R.T., Nishele Lenards, M.S., CMD, R.T.(R)(T), FAAMD,
Anne Marie Vann, MEd, CMD, RT(R)(T), FAAMD
Abstract
Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of nonHodgkins lymphoma; successfully treated when radiation therapy is delivered after
chemotherapy. The purpose of this case study was to evaluate the radiation therapy protocol and
dose regimen for a patient with an extensive left thigh DLBCL tumor that encased the femoral
neurovascular bundle and caused venous compression.
Case Description: The case study involved a patient with a significantly large lower leg tumor
treated with a classical AP/PA 3D-CRT extended SSD set up combined with a field-in field
technique for better dose homogeneity due to different tissue thicknesses. In order to reduce the
chemotherapy induced toxicities, the consolidation involved-field radiotherapy (IFRT) technique
was delivered post abbreviated chemotherapy. The IFRT included the positron emission
tomography (PET) volume, the clinical target volume (CTV) delineated by the radiation
oncologist, and the planning target volume (PTV) that was created by adding a 1 cm margin to
the CTV. The field-in field segment method was used to obtain better dose conformity.
Conclusion: Based on previous studies, the IFRT has higher survival rate than chemotherapy
alone. The goal of this plan was to achieve the physician prescription of 4000 cGy to the tumor
volume. The extent of the tumor created difficulties in achieving the best outcome, and this led to
a compromise in the dose distribution. Alternate treatment considerations included the use of
bolus over the leg and intensity modulated radiation therapy (IMRT) as a treatment delivery
technique. Neither option was determined viable for this patient case.
Key Words: Diffuse Large B-Cell Lymphoma, Non-Hodgkins Lymphoma, involved-field
radiotherapy (IFRT), 3D-CRT

Introduction
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkins
lymphoma (NHL) at approximately 30-40 % in the adult population.1 This type of neoplasm is
more prevalent in the elderly population manifested by enlarged lymph nodes with an aggressive
tendency for growth.2 Non-Hodgkins lymphomas can appear anywhere in the body where

2
lymph travels. It could be found in the lymph nodes, organs where the lymph goes to, or both.
Non-Hodgkins lymphoma spreads in a random manner without a specific pattern. Often there
are several organs and groups of lymph nodes affected by this disease. The average patient age is
67 years. It is slightly more predominant in males than females. In the United States, more white
males are diagnosed with NHL in comparison with other races, such as African-Americans,
Asians, Hispanics or Native Americans. Since 1970, the number of newly diagnosed patients has
increased approximately 65% and continuously growing. The exact reasons for this are
unknown. Research studies linked such cases as genetic defects, exposure to ionizing radiation,
lower immunity and contacting various infectious factors.
The prognosis of DLBCL is better for young patients; however the average age at
diagnosis is late sixties and the elderly population had a less than satisfying response to
treatments. From a histological perspective, non-Hodgkin lymphomas are classified as follicular
also named nodular, or diffuse. The follicular type originates from B cells and appears most of
the times below the diaphragm and involves the lymph nodes of the mesentery. The diffuse NHL
originates from B or T cell types and it has a tendency to spread more aggressively to other sites
in the body. The most common is the spread to the lymphatics.
Treatment for DLBCL is controversial. This type of cancer can be deadly but it has
chances to be curable.3,4 It can be eradicated nowadays in more than 50% of the patients.
Determining the proper treatment requires a precise diagnosis. Studies have stressed the need of
excisional biopsy versus the fine needle aspiration, and the evaluation of tissue by a
hematopathologist to provide the most accurate diagnostic.3 Chemotherapy with administration
of radiation therapy to patients who present with bulky disease seems to be a successful
treatment method with prolonged survival rates. For patients with chemotherapy-sensitive
relapse the best option is to undergo autologous stem cell transplantation.
The role of consolidation radiation therapy treatment for patients diagnosed with DLBCL
is important and needs to be acknowledged. Studies review this topic and debate it in the
literature.5 The risks versus benefits of treating patients with radiation therapy have been
carefully analyzed and discussed. The consolidation IFRT delivered post abbreviated
chemotherapy technique was chosen for the case patient to reduce the chemotherapy induced
toxicities. In a Phase II clinical trial conducted by Southwest Oncology Group (SWOG), the
implementation of the IFRT after chemotherapy was studied for 60 DLBCL patients.6 After a

3
careful selection of the participants, the radiation therapy treatment was delivered three weeks
after the end of the chemotherapy and the dose delivered ranged between 40 to 46 Gy, in daily
fractions of 180 cGy, 5 days per week. The purpose of the study was to evaluate the disease
progression free survival (PFS) for the participants. The results concluded an increased
percentage of patients without any DLBCL evolution, respectively 95 % of 2 years and 92 % of
4 years. These results were compared with a previous study involving only chemotherapy that
had PFS percentages of 78% at 2 years and 88% at 4 years. This was a randomized trial that
involved patients who demonstrated a complete response after six cycles of chemotherapy.8
These patients received radiotherapy or no other treatment. The results did not demonstrate a
benefit in using this technique. However, in patients with bulky disease, the consolidated IFRT
significantly improved the relapse-free survival rate. Other studies researched the impact that
fluorodeoxyglucose-positron emission tomography (FDG-PET) in diagnosing and staging of
DLBCL followed by IFRT, which could lead to improved progression free survival for the
patients.7 The use of the FDG-PET scan is particularly useful in the relapse situations.
There is a new concept of involved-node radiotherapy (INRT) for the treatment of
DLBCL, and its purpose is to reduce the radiation therapy toxicities.5 When treating patients
with limited DLBCL, reducing the field size of IFRT to INRT less than or equal to 5 cm, can
maintain a good margin for the recurrence risk and reduce the radiation toxicities. Involved-node
radiotherapy is supposed to be delivered to the pre-chemotherapy nodes, as well as taking into
account the potential primary relapse sites, which can be infield, marginal or distant to the
treated field.
This case study focuses on the consolidated IFRT for a patient diagnosed with diffuse
large B-cell lymphoma. A classical radiotherapy patient set up was used with field-in-field
segment technique to obtain an optimal dose distribution for a large tumor that encompassed the
pelvis and the entire left leg.

Case Description
Patient Selection
A 52 year old male presented to the emergency department with left lower leg edema. He
reported that approximately 3 months prior, he suffered blunt trauma to the left inguinal region
with a heavy box. The pain and the edema had increased over 2 weeks. The patient was

4
hospitalized and had computed tomography (CT) and magnetic resonance imaging (MRI) scans
completed. The results revealed an extensive long segment left thigh mass with internal cystic or
necrotic components, encasing the left superficial femoral neurovascular bundle extending from
the pelvis to the knee. The thigh was enlarged with subcutaneous soft tissue edema. The tumor
caused venous compression, abutted the bladder and invaded the left seminal vesicles. A needle
core biopsy was performed of the left inguinal lymph nodes. The pathology demonstrated diffuse
large B-cell lymphoma, with a high proliferation index (70%). Another CT was performed of the
chest, abdomen and pelvis with IV contrast demonstrating no evidence of metastatic disease. The
patient also complained of scrotal swelling, therefore an ultrasound scrotal exam was performed,
which demonstrated edema to the scrotal wall. After the initial diagnostic studies, the radiation
oncologist recommended chemotherapy, followed by an MRI exam to the brain and a positron
emission tomography (PET)/CT to determine the response to the chemotherapy.
Patient Set Up and Target Delineation
The patient underwent a CT simulation utilizing a Phillips large bore CT simulator. An
Alpha Cradle mold was used to immobilize the legs in place. The patient was positioned supine,
feet towards the gantry and hands on the chest (Figure 1). Anterior and lateral markers were
placed on the patients body, at the pelvis level to ensure set up reproducibility for treatments.
After the CT simulation, the data was imported to the Varian Eclipse 11.0 treatment planning
system. There were three CT scans used for this patient. The PET/CT scan completed during
work-up was fused with the CT simulation. The radiation oncologist evaluated the prechemotherapy CT scan and delineated the Planning Target Volume (PTV), which included the
PET positive areas and the Clinical Target Volume (CTV). A 1 cm margin was added to the
CTV in order to determine the PTV to be treated (Figure 2).
Treatment Planning
Following chemotherapy, consolidative radiation therapy with a curative intent was
recommended. The consolidative therapy is used to eliminate any remaining cancer cells in the
body after the initial treatment completed. The radiation oncologist prescribed a total of 40 Gy to
be delivered in 20 fractions at 2 Gy/fx, using 6 MV. The tumor extended over a significantly
long area. The radiation oncologist planned to spare the edematous skin; therefore bolus was not
used for this patient. For the megavoltage beams, the dose distribution can be successfully
delivered to the deep seated tumors, while sparing the skin.9 To avoid matching fields with

5
junctions, the extended source to skin distance (SSD) method was used. The purpose was to treat
the area in one large AP and PA field and to avoid areas of overdose or underdose that may
occur with field junctions or the gap technique. Potential positioning errors and difficulties that
might occur during treatments were also taken into consideration, leading to the decision of the
extended SSD set up. A 130 cm SSD was set for both AP and PA fields to include the entire
volume in the treatment field. The gantry was set at 0 degrees for the AP field, and 180 degrees
extended (180-E) for the PA field. For both fields, the collimator angle was set at 0 degrees.
The radiation oncologist reviewed the field sizes and shielded the areas at risk (Figures 3
and 4). The field sizes exceeded the accepted limits to use the enhanced dynamic wedge (EDW).
To compensate for the missing tissue, the field-in-field technique was utilized. The extent of the
tumor and the differences in thickness between the proximal thigh, pelvis area, and the distal
lower leg, created a heterogeneous dose distribution along the treatment field. To even this
heterogeneity of the dose, two segment fields were created, one for the AP position and one for
the PA (Figures 5 and 6). These fields were weighted 0.07 for the AP and 0.05 for the PA. The
field-in-field technique improved the dose homogeneity within the treated volumes by
decreasing the high dose areas. The radiation therapists were instructed to position the AP set up
field to 95 cm, according to the set up instructions. After filming, the table was to be lowered 35
cm to reach the 130 cm SSD for treatment for the AP field. For the PA field, the couch was to be
raised up to the given index corresponding to the 130 SSD. The planning parameters and beams
weighting are listed in Table 1.
Plan Analysis & Evaluation
Due to the extent of the tumor, and the differences in thickness of the treated volume, it
was difficult to get a homogenous dose distribution throughout the entire tumor volume. The
plan was normalized for 100% of the dose to cover 92% of the PTV. The radiation oncologist
prescription was 4000 cGy to the tumor volume. No other organs at risk were delineated for this
patient. After careful evaluation of the dose volume histogram (Figure 9), the following
structures were determined to receive the following doses: the PET positive volume received
100% of the dose, the CTV received 99 % of the dose, and 92% of the PTV volume was covered
by 100% of the dose. As seen in Figures 7 and 8, the dose distribution was not ideal. The mean
dose for the PTV was 4300.5. The hot spot reached 4773.8 cGy; however the distribution was
the best that could be achieved for this case and the radiation oncologist accepted the plan. As

6
seen in the dose volume histogram, 92% of the PTV received 100% of the dose. (Figure 10) The
dose evaluation is listed in Table 2.
Conclusion
The purpose of this case study presentation was to demonstrate the applicability of the
IFRT for the treatment of diffuse large B-cell lymphoma (DLBCL) and to describe the classical
AP/PA 3D-CRT approach in combination with the field-in-field technique in radiation therapy
treatment planning to achieve the desired dose coverage. There were difficulties in obtaining the
desired result; therefore a compromise was accepted with regard to the dose distribution. The
intensity modulated radiation therapy (IMRT) technique was not considered for this plan, due to
the fact that no organs at risk were in the area of the treatment. The radiation oncologist
evaluated the patients medical history, the complexity of the disease, the proximity of the tumor
to the skin surface, and the extensive treatment volume. For all these reasons, IMRT was not
considered in this situation. The skin toxicity can be high with IMRT, especially when the
tumors are not deep seated.10 Encompassing the pre-chemotherapy lymph nodes in the PTV,
extent of the disease, large field sizes, and the high proliferation rate for this case make this
patient a good candidate for the IFRT technique. Further research and clinical studies may reveal
better treatment options and improve the survival time for the DLBCL patients.

References
1. Qi SN, Li YX, Wang H, et al. Diffuse large B-cell lymphoma. Cancer. 2009;115(21):4980
4989. http://dx.doi.org/10.1002/cncr.24557
2. Washington CM, Leaver D. Principles and Practice of Radiation Therapy. 3rd ed. St. Louis,
MO: Mosby Elsevier; 2010.
3. Armitage JO. My Treatment approach to patients with diffuse large B-cell lymphoma. Mayo
Clinic Proceedings. 2012;87(2):161171. http://dx.doi.org/10.1016/j.mayocp.2011.11.007
4. Biswas T, Dhakal S, Chen R, et al. Involved field radiation after autologous stem cell
transplant for diffuse large B-cell lymphoma in the Rituximab era. Int J Radiat Oncol Biol
Phys. 2010;77(1):7985. http://dx.doi.org/10.1016/j.ijrobp.2009.04.036
5. Campbell BA, Connors JM, Gascoyne RD, et al. Limited-stage diffuse large B-cell
lymphoma treated with abbreviated systemic therapy and consolidation radiotherapy involved-field versus involved-node radiotherapy. Cancer. 2012;118(17):4156-4165.
http://dx.doi.org/10.1002/cncr.26687
6. Persky DO, Unger JM, Spier CM, et al. Phase II study of rituximab plus three cycles of
CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell
lymphoma: Southwest Oncology Group study 0014. J of Clin Onc. 2008;26(14):2258-2263.
http://dx.doi.org/ 10.1200/JCO.2007.13.6929
7. Hoppe BS, Moskowitz CH, Zhang, Z, et al. The role of FDG-PET imaging and involved field
radiotherapy in relapsed or refractory diffuse large B-cell lymphoma. Bone Marrow Transpl.
2009;43(12):941-948. http://dx.doi.org /10.1038/bmt.2008.408
8. Aleman BMP, Raemaekers GMM, Tirelli U, et al. Involved-field radiotherapy for advanced
Hodgkin's lymphoma. N Engl J Med. 2003;348(24):2396-2406.
http://dx.doi.org/10.1056/NEJMoa022628
9. Butson MJ, Cheung T, Yu P, Metcalfe P. Effects on skin dose from unwanted air gaps under
bolus in photon beam radiotherapy. Radiation Measurements. 2000;32(3):201-204.
http://dx.doi.org/10.1016/S1350-4487(99)00276-0
10. Lee N, Chuang C, Quivey JM, et al. Skin toxicity due to intensity-modulated radiotherapy for
head-and-neck carcinoma. Int J Radiat Oncol Biol Phys. 2002;53(3):630-637.
http://dx.doi.org/10.1016/S0360-3016(02)02756-6

8
Figures

Figure 1. Patient set up position in the CT simulator lateral view.

Figure 2. PTV delineation in red and PET positive volume in light green.

Figure 3. AP field in beam eye view with multileaf collimator (MLC)

10

Figure 4. PA field in beams eye view with multileaf collimator (MLC)

Figure 5. AP segment field in beams eye view with multileaf collimator (MLC)

11

Figure 6. PA segment field in beams eye view with multileaf collimator (MLC)

12

Figure 7. Dose distribution in dose color wash coronal view.

13

Figure 8. Dose distribution in dose color wash sagital view.

14

Figure 9. Dose volume histogram (DVH).

15
Tables
Table 1. Summary table including the treatment planning parameters.
Treatment Planning Parameters
Prescription

4000 cGy in 20 Fx

Fields

AP

AP Segment

PA

PA Segment

AP Set Up

Size (cm)

11.4 x 40

13.9 x 20

11.6 x 40

14 x 20

20 x 20

Gantry Rotation

180 E

180 E

Beam Energy

6 MV

6 MV

6 MV

6 MV

6 MV

SSD

130 cm

130 cm

130 cm

130 cm

95 cm

Beam Weighting

0.43

0.07

0.43

0.05

Table 2. Summary table including evaluation of the dose delivered to the structures delineated in
the plan.
Dose Evaluation to the Contoured Structures
Prescription
(cGy)

Max Dose
(cGy)

Mean Dose
(cGy)

% Vol
receiving 100%
of dose

PTV

4000

4773.9

4300.5

92%

CTV

4000

4773.9

4386.9

99%

PET Positive Volume

4000

4660.4

4393.9

100%

Pre Chemo Volume

4000

4773.9

3667.1

76%