Transcript PET-CT Evaluation of Lymphoma

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Fluorodeoxyglucose (FDG), as a glucose
analog, is taken up by high-glucose-using
cells such as brain, kidney, and many types of
cancer cells, where phosphorylation prevents
it from being released again from the cell,
once it has been absorbed
18Fluorine: Positron emitter
 T1/2 110 minutes
FDG-PET/CT findings can result in a change in patient
staging up to 44% of patients (either up-stage or
down-stage
 FDG-PET/CT exams findings result in a change in
patient management in up to 62%
 FDG-PET/CT imaging can be positive in up to 50% of
patients felt to be in complete remission
 FDG-PET/CT has been shown to be more sensitive
and specific than CT imaging alone for staging and
restaging lymphoma (particularly for organ
involvement, such as infiltrative disease in the spleen,
liver, and bone marrow which may be radiographically
occult)
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Staging
 Stage before any treatment started; one dose of
chemo may decrease uptake, causing
underestimation of stage
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Assessment for tumor recurrence
Differentiate scar from residual tumor mass
Monitor response to therapy
Predict outcome
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Negative FDG uptake in lesion following therapy
 high predictive value for disease-free survival
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Persistent FDG uptake after treatment
 moderate predictive value for recurrence
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Mid-cycle evaluation
 Allow change in therapy in high risk patients or those
with no symptomatic improvement
 Avoid unnecessary toxicity if treatment not working
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Imaging post-therapy allows treatment of
residual disease to prevent spread
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Patients who do not respond to initial chemotherapy
are candidates for salvage chemotherapy or
autologous bone marrow transplantation
Recognition of resistant or nonresponding tumor
early during chemotherapy may result in lower
cumulative treatment toxicity and tumor burden at
the start of salvage therapy, thereby potentially
improving clinical outcome and prognosis.
Usually, metabolic changes following therapy tend to
precede anatomic changes, a phenomenon that
allows early response evaluation with functional
imaging
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Effective treatment sharply reduces
metabolic tumor activity within days,
whereas persistent abnormal uptake is
usually associated with treatment failure
In addition, interim PET performed after one
or two cycles of chemotherapy may help
predict long-term freedom from relapse
more accurately than posttreatment PET,
which does not help exclude the presence of
microscopic residual disease
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Lymphoma represents many different cancers of
lymphocytes (about 35 different subtypes)
Lymph nodes are small collections of lymph
tissue that occur throughout the body
The lymphatic system involves lymphatic
channels that connect thousands of lymph
nodes scattered throughout the body
Lymph flows through the lymph nodes, as well
as through other lymphatic tissues including the
spleen, the tonsils, the bone marrow, and the
thymus
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Lymphocytes recognize pathogens (infections and abnormal
cells) and destroy them
There are 2 major subtypes of lymphocytes
 B lymphocytes (B cells) produce antibodies (proteins that circulate
through the blood and lymph and attach to infectious organisms and
abnormal cells); which alerts other cells of the immune system to
recognize and destroy these pathogens
 T lymphocytes (T cells), when activated, can kill pathogens directly
▪ play a part in the mechanisms of immune system control, to
prevent the system from inappropriate overactivity or underactivity
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Lymphoma is a malignant transformation of either
lymphocytes B or T cells or their subtypes
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Stage I
 limited to a single lymph node or lymph node group
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Stage II
 Disease in 2 or more lymph node groups on the same side of the diaphragm
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Stage III
 Disease in two or more lymph node groups on both sides of the diaphragm
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Stage IV
 disease in extranodal sites such as the lung, liver, bone or bone marrow,
spleen, or other
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Special Qualifiers
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X: Bulky disease with nodes larger than 10 cm
A: The patient has no symptoms
B: The patient has symptoms such as fever, weight loss, or night sweats
E: Extranodal
S: Splenic involvement
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Early Favorable
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stage I or stage II, without risk factors.
Early Unfavorable
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stage I or stage II with one or more of the following risk factors:
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A tumor in the chest that is larger than 1/3 of the width of the chest or at least 10 centimeters
A high sedimentation rate (in a sample of blood, the red blood cells settle to the bottom of the test tube
more quickly than normal).
Three or more + lymph nodes
Symptoms such as fever, weight loss, or night sweats.
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Being male.
Being aged 45 years or older.
Having stage IV disease.
Having a low blood albumin (protein) level (below 4).
Having a low hemoglobin level (below 10.5).
Having a high white blood cell count (15,000 or higher).
Having a low lymphocyye count (below 600 or less than 8% of the white blood cell count)
Advanced Favorable is stage III or stage IV with three or fewer of the following
risk factors and Advanced Unfavorable is four or more of the following:
HIV-related HD more aggressive
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IA-IIA: short course chemotherapy with involved-field
XRT
III, IV A-B: combination chemotherapy alone
R-CHOP
 Rituxan:chimeric monoclonal antibody against the protein
CD20, which is primarily found on the surface of B cells
 CHOP:
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Cyclophosphamide (also called Cytoxan/Neosar)
Doxorubicin (or Adriamycin)
Vincristine (Oncovin)
Prednisolone
R-EPOCH: same as R-CHOP, with Etoposide
Hodgkin lymphoma is one of the most common malignant
neoplasms in young Americans with 7500-8000 new cases
annually in the US
 Bimodal age distribution: late 20's and > 50 yrs
 Risk Factors:
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 Epstein Barr virus; Reed-Sternberg cells
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(RS) infected with EBV in 50%
HIV
Being in young or late adulthood
Being male
Having a first-degree relative (parent, brother, or sister) with HL
Core biopsy needed for diagnosis; RS cells not large in
number, scattered
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Histologic Types:
 Classic
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Nodular sclerosing (most common form)
Mixed cellularity (second most common form)
Lymphocyte predominant (favorable prognosis)
Lymphocyte depleted (worst prognosis)
Other
 Nodular Lymphocyte Predominance
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Stage at presentation and tumor cell type
determine overall prognosis and optimal
method for treatment
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Anatomic extent of disease is the single most
important factor influencing relapse-free
duration and overall survival
The 5 year survival for stages I and IIA are
close to 90%, and even in advanced stage
disease (stage IVA or IVB) the survival can be
as high as 70%
Spreads in a contiguous manner to other LN’s
then to viscera and marrow
Stage III Hodgkin
lymphoma
Typical appearance of postchemo axial marrow
Stage IIA Nodular
Sclerosing HL
22 yo old presented with right
neck mass, otherwise
asymptomatic
Complete mid-cycle chemo
response
History of mononucleosis
confirmed with Monospot one
year earlier
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Estimated new cases and deaths from NHL in the United
States in 2009:
New cases: 65,980
Deaths: 19,500
Heterogeneous group of lymphoreticular malignancies that
differ with regard to histopathology, clinical behavior,
response to therapy, and clinical outcome
NHL's include diffuse large B-cell (31%), follicular (22%),
marginal zone or MALT (8%), peripheral T-cell (7-15%), small
lymphocyte B-cell (7%), mantle cell (6%), and others (11%)
Treatment for NHL is based on several factors, including
tumor grade
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Direct correlation between the degree of FDG
uptake and the histologic grade of lymphoma
 High-grade tumors demonstrate greater metabolic activity (and
greater FDG accumulation) than low grade
 Low-grade lesions (including mucosa-associated lymphoid
tissue lesions) may not accumulate sufficient FDG to be
detected
 Other subtypes of lymphoma that are poorly FDG avid on PET
include marginal zone lymphoma and peripheral T-cell
lymphoma
Low grade NHL accounts for about 40% of new cases
Indolent course
Most patients are treated with single-agent
chemotherapy or conservative watching and waiting
 FDG-PET imaging may have only a limited role in
managing patients with low-grade lymphoma
 The presence of residual disease after treatment may
not be clinically relevant as this type of lymphoma
generally has no cure, but is indolent with a survival of
10-12 years
 PET may play a role in evaluation of these patients
should transformation to a higher-grade lymphoma
occur (10%-20% of cases)
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About 40% of new cases
Treatment consists of combination
chemotherapy and involved-field radiation for
patients with bulky disease or early-stage nonbulky disease
The role of FDG-PET imaging in patients with
intermediate grade lymphoma would be to
demonstrate disease extent and therapy
response, with hopes for improved survival with
early modifications in chemotherapeutic
regimens
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High-grade NHL accounts for 5%-10% of new
cases
Untreated, high-grade NHL is associated with a
survival measured in weeks
Treatment consists of aggressive combination
chemotherapy
With treatment, remission can be achieved in
about 60% of patients
High grade lymphomas are very FDG avid and
PET imaging can be used for staging and
monitoring response to therapy
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T-cell NHL’s include mycosis fungoides,
anaplastic large cell lymphoma, and
precursor T-lymphoblastic lymphoma
T-cell lymphoma has an overall poor
prognosis, with a 5-year survival rate of about
15-30%
T-cell NHL can be divided into peripheral and
leukemic subtypes
Most T-cell lymphomas are FDG positive, but
indolent lesions will show lower FDG uptake
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Peripheral TCL, unspecified
 Most common subtype of TCL accounting for 60-70% of cases
 Generalized lymphadenopathy is the most common finding
 Almost all lesions show high FDG accumulation
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Angioimmunoblastic TCL:
 Accounts for 15-20% of cases of TCL
 typically present with advanced disease (overall median survival
is 15 months)
 Nodal involvement is associated with organomegaly, Bsymptoms, rash, puritis, pleural effusion, arthritis, and
eosinophila
 Sensitivity of FDG PET for the detection of extracutaneous
lesions approaches 100%
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Cutaneous TCL
 Mycosis fungoides (typically indolent)
 Sezary syndrome (sometimes considered a late stage
of mycosis fungoides)
 Progression to involve lymph nodes and viscera
 The 5-year survival decreases from 90% for cutaneous
only disease, to almost 0% for disease with visceral
involvement
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Anaplastic large cell cutaneous type TCL
 Indolent disorder (85% 10-year survival)
 Affects older adults
 One of the least FDG avid TCL's
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Natural killer nasal and nasal type TCL
 Aggressive lesion
 Strong association with EBV
 Variably FDG avid
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Enteropathy-type TCL
 Affected patients typically have a history of
gluten-sensitive enteropathy and the disorder
carries a poor prognosis
 FDG PET is more sensitive than CT
NHL with pancreatic
and renal involvement
65 yo female presented with
early satiety and nausea
Complete response to
R-EPOCH
Diffuse B Cell
Lymphoma
29 yo old female with enlarging
thyroid for 1 yr, with bilateral
vocal cord paralysis
Referred for RAI ablation, but 3
hr uptake was 0.8% and 24 hr
uptake was 0.5%
Patient underwent subtotal
thyroidectomy where
lymphoma was discovered
Staging PET/CT shows FDG
avid adenopathy neck, chest
abdomen, pelvis with
nonspecific FDG avid
consolidation
T Cell Acute
Lymphoblastic
Lymphoma
26 yo old male relapsed after 4
cycles chemo (about 5-6
months after presentation)
Originally presented with rib
pain, SOB, fatigue
Initially responded well to
chemo with resolution of
effusion and FDG uptake
shortly after chemo started
Diffuse Large B Cell
Lymphoma
Status post R-EPOCH x 7 with
XRT
FDG-PET/CT shows no
significant activity despite
some residual soft tissue
Mildly elevated marrow, likely
from chemo and/or anemia
Diffuse Large B Cell
Lymphoma of the
Elderly
66 yo male with ulcerative
perianal lesion
Pathology revealed EBV
positivity
No spread of disease at staging
Complete response to RCHOP
and will be scheduled for
involved-field XRT
Extranodal
Involvement: Marrow,
Lung
Lung, marrow, nodal
involvement
Stage 4 NHL
Cytokine Effect on
Marrow FDG Uptake
Large Cell Lymphoma with
gastric, hepatic disease
Spleen and marrow uptake has
DDX cytokine effect vs. disease
involvement
Bone-marrow response to GCSF decreases rapidly following
the last CSF administration.
Therefore, FDG-PET in patients
receiving G-CSF should be
delayed, when possible, until 5
days after the end of G-CSF
therapy
Extranodal
Involvement: Marrow
Lymphomatous infiltration in a
30-year old woman with
relapsed Hodgkin disease
Extranodal
Involvement: Bone
and Liver
B-cell non-Hodgkin's
lymphoma
Extensive hepatic involvement
Focal bone disease such as this
will not be detected on bone
marrow biopsy
Extranodal
Involvement: Spleen
On FDG PET imaging, diffuse
or focal splenic uptake of
greater intensity than the liver
is felt to represent tumor
involvement
Infiltrative lymphomatous
involvement of the spleen can
be detected with a 67%
increased frequency when
compared with CT imaging
In this example, enhanced CT
shows no splenic abnormality,
but spleen FDG is diffusely
increased relative to liver
Extranodal
Involvement: Spleen
16 yo with Stage IVB Nodular
Sclerosing HL
Splenic involvement despite
no clear-cut CT abnormality
Extranodal
Involvement: Spleen
Diffuse spleen
involvement is detected by
FDG PET; CT negative
Most PCNSLs are diffuse large B cell NHL’s
Primarily in patients with severe
immunosuppression
 Represent around 20% of all cases of
lymphomas in HIV infections (other types are
Burkitt's lymphomas and immunoblastic
lymphomas)
 Highly associated with EBV infection (> 90%) in
immunodeficient patients
 Does not have a predilection for any particular
age group
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PCNSL
HIV+ patient with mental
status changes
Biopsy-proven Large B Cell
NHL
 90Y-ibritumomab tiuxetan (Zevalin)
 IgG1 kappa-monoclonal antibody directed against the
CD20 antigen that is found on normal mature Blymphocytes and on more than 90% of malignant Blymphocytes in patients with B-cell non-Hodgkins
lymphoma
 Approved for treatment of relapsed or refractory low
grade follicular, or CD20+ transformed NHL when
marrow involvement is not more than 25% (as
measured by bone biopsy)
 90Y: pure beta emitter that decays to 90Zr with a half
life of 64 hours (2.7 days)
 131I-tositumomab (Bexxar)
 Anti-B1 murine monoclonal antibody that binds to the
CD20 antigen expressed on the surface of malignant
B-lymphocytes
 Used in the treatment of non-Hodgkin's lymphom
 I-131 gamma emission can be used for documentation
of the biodistribution of the agent and to calculate a
patient-specific dosage to deliver the desired
therapeutic radiation
 Thyroid blockage is required due to release of 131I from
the antibody. A saturated solution of potassium iodide
(SSKI or Lugol's) is given from the day before the
treatment until 14 days following therapy
RIT efficacy assessed
by FDG-PET
Pre-treatment FDG PET
imaging showed diffuse lymph
node involvement (right
axillary, lumbar, right and left
iliac and right inguinal on
slices).
FDG-PET performed 6 weeks
after RIT showed a metabolic
complete response
Tumor response to
radioimmunotherapy
may be more gradual than
response to
chemotherapy.
FDG PET metabolic data
obtained 1–2 months after RIT
may correlate well with
the ultimate response of nonHodgkin lymphoma
to RIT
False Positive FDGPET Findings in
Lymphoma Patients
Sarcoid, TB
Thymus and Thymic Rebound
in young patients
False positive FDGPET
Lung toxicity from
chemotherapy
Increased FDG uptake due to
G-CSF therapy in a 49-year-old
woman with a history of nonHodgkin lymphoma and bone
marrow transplantation.
Whole-body PET scan shows
diffuse increased FDG
uptake in the bone marrow and
spleen
XRT Pneumonitis
Radiation pneumonitis in a 26year-old man with NHL who s/p
XRT 4 months earlier. PET scan
shows intense FDG uptake in
the medial chest and CT shows
consolidation in the
paramediastinal lung
The accumulation of FDG in
tumor cells may be
enhanced following radiation
therapy; XRT may cause
inflammation in normal
structures such as the lungs
and mucous membranes,
thereby inducing pneumonitis
pharyngitis, and esophagitis
Generally, FDG uptake 6
months after radiation therapy
is associated with tumor
recurrence; variable
Physiologic Brown Fat
Metabolism
Brown fat (unlike white adipose
tissue fat) contains a large
number of mitochondria and has
the capacity to generate heat
Brown fat is stimulated by several
factors, including exposure to
cold (decreasing body
temperature) which causes overexpression of glucose transporter
4 in brown fat; incidence of
uptake in brown fat has been
shown to be increased during
periods of cooler temperatures ;
also brown fat activation by the
sympathetic nervous system
(catecholamine stimulation)
Administration of fentanyl,
diazepam, or the use of a low
high-fat, low-carbohydrate, and
protein permitted diet may also
reduce FDG uptake by brown fat;
warming
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Small size of lesion < 1 cm
Steroids can lead to lower FDG accumulation
in malignant lymphoma than in the
surrounding tissue as a result of their antiinsulin effect on carbohydrate metabolism
Obscuration by physiologic activity; brain,
kidney, bladder
Nonspecific physiologic uptake; bowel