TOPICS
Clinical Use - Overview
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Preparations
| PET
safety |
False Positives
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Summary of
Uses &
Limitations
| Response to Treatment |
SUV Reference
Range |
Resources
| Research News
TOPIC SEARCH:
PubMed
In the News:
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PET scans: when and how?
http://bit.ly/qQPoCk
James Olen Armitage |
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About PET scans
(2010, sponsored by LRF) |
Normal PET scan =>
PET Overview:
PET stands
for Positron Emission
Tomography.
After treatment, doctors use a PET scan to see if the visible tumors
are taking up the PET tracer.
The PET tracer is injected into the blood prior to the scan.
The PET tracer has two parts: glucose, and a mildly radioactive
component.
As the tracer moves through the body the cells that
are active take up the glucose along with the radioactive part
of tracer.
Tumor cells are
generally
metabolically active (hungry) and will take up more sugar (glucose) than
normal cells. The more
glucose the cells take up, the more the cells light up.
PET scans take advantage of this
difference to help distinguish active from inactive tumor masses.
Injecting the PET
tracer into your body allows
special cameras to show cells that take up excessive glucose - cells such as malignant cells, but also reactive normal cells, that have a higher metabolic rates.
LIMITATIONS: While cancer cells often take up more glucose than
normal cells, sometimes normal cells take up high amounts of glucose
too.
Individual cancer cells that make up a visible tumor
are too small to see by CT or PET scans. So we can’t know for
sure if the disappearance of the majority of cancer cells (the
visible tumor) or a decrease in the uptake of the glucose-based
tracer in the remaining cells in the tumor area means that all the
cancer cells have been killed by the treatment.
"Although CT and MRI provide high-resolution anatomic information, PET adds information on the metabolic activity of lesions.
Standardized uptake values (SUVs) are a measure of the concentration of a radiotracer in a defined region divided by the injected dose normalized for the patient's body weight at a fixed time after tracer injection.
This functional information may be particularly useful in determining response to therapy, as suggested by the European Organization for Research (25). These metabolic changes may occur even if anatomic size
of the tumor does not change significantly."
2
Clinical
Use of
PET-based imaging in lymphoma -
"very little is
actually certain and agreed upon."
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Based on Lymphoma Type and Clinical Setting |
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PET-based
imaging for: |
Aggressive |
localized
suspected |
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Indolent - |
transformation concern |
Hodgkin |
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Initial Staging |
Most do |
Most do |
Controversial, but
Most do |
Most do |
Most do |
Interim treatment
response |
Investigational |
- |
Investigational |
- |
Predictive, but investigational |
Post treatment
response |
YES |
- |
Controversial, but
Most do |
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YES |
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Surveillance |
Most don't |
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Most don't |
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Most don't |
On the clinical use of PET-based imaging in
lymphoma:
Dr. Rebecca Elstrom kindly shared her perspective:
"I suspect you will get different answers to
these issues, which suggests that very little is actually
certain and agreed upon.
I would venture that the only thing just about everyone agrees
on is PET for post-treatment response assessment in Aggressive
and Hodgkin lymphomas (not indolent--this is still controversial
and many still argue that CT is just as good for standard care,
though many patients get it anyway).
For initial staging, most do PET for aggressive and Hodgkin,
though it rarely changes management and some experts argue that
it is unnecessary.
PET in indolent lymphoma would be considered appropriate
pre-treatment mostly in 2 settings: if thought to be localized
with potential for cure with radiation, or if there is concern
for transformation. Although in practice many patients get them
anyway, most patients with known advanced stage, "normal"
presentation indolent lymphomas do not necessarily need a PET.
Interim therapy PET is investigational in all settings. Although
proven to be predictive in Hodgkin, we don't yet know what to do
with the information (studies are ongoing and we should have
answers soon). For DLBCL, positive vs. negative PET is not
predictive, but studies are evaluating the potential utility of
quantitative assessment (i.e. whether a percentage decrease in
SUV, or intensity of uptake of the tracer, is predictive). For
indolent lymphoma, there is minimal information.
Most would agree that PET should not be used for surveillance*
due to high incidence of false positives, though a small
minority of investigators would disagree."
* Examples of surveillance would be so-called watch and wait
(observation of indolent lymphoma), but also observation after
therapy with curative intent – such as regularly scheduled
monitoring of patients with aggressive or Hodgkin lymphoma after successful
therapy.
Lack of Standard Protocols for PET
PET protocols are
not yet standardized in regular
practice -- that is, it can be done differently at various
centers, which can affect the SUV readings:
(1) the dose of the
tracer,
(2) the length of the scan,
(3)
your blood sugar levels,
(4) how long after therapy,
(5)
the type of therapy (chemo / Rituxan / RIT) ...
all
can influence the readings. So it's not yet an exact science.
Generally, concern
increases if the SUV in one tumor region is
many times greater than in another tumor area ... but your
doctor will know about this and discuss this if it is.
Inflammation can also cause higher SUV
readings. So PET is not used to diagnose a lymphoma, but it
can help guide where to biopsy. For example, the surgeon will remove (if feasible /
safe) the node with the highest SUV to increase the chance of
getting a reliable diagnosis.
The use of PET to
judge if a treatment is effective early
(after one or two rounds of therapy) will require standardized
methods of using PET -- and clinical research to confirm that the test
can be used reliably for this purpose for the different subtypes of
lymphoma.
Advocacy note:
patients might be provided with a procedure checklist as a
quality control -- to help improve compliance with standards for
administering a PET in general practice, should this use of PET
be confirmed as clinically useful by well-designed clinical
trials.
Following completion
of treatment the use of PET to determine if residual masses visible
by CT imaging is viable (still lymphoma) or is scar tissue is widely
considered conclusive for that region.
More detail on the PET tracer:
FDG (2-Fluoro-2-Deoxy-D-Glucose) is a positron
emitting radio-pharmaceutical. FDG emits positrons that make
gamma rays which the PET scanner detects. It's half life is about
110 minutes. So you will pose no risk to others shortly after
the test is done - about 1.2 hours.
(Corrected definition submitted kindly by Dr. Williams)
Search for
ACR
accredited Diagnostic Imaging Centers
ACR accreditation
means:
"Your hospital, clinic or health center has
voluntarily gone through a rigorous review process to be sure it
meets nationally accepted standards. The personnel are well
qualified, through education and certification, to perform and
interpret your medical images and administer your radiation
therapy treatments. The equipment is appropriate for the test or
treatment you will receive, and the facility meets or exceeds
quality assurance and safety guidelines."
Preparation for PET may vary at
different centers
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You will be asked to fast before
the PET scan. |
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Regarding your last meal before
the scan:
Choose foods high in protein; low in carbohydrates,
Avoid sweets, breads, pasta, rice, and cereals.
Do not eat anything for at least 6 hours prior to your
exam.
Most medications do not interfere with this test and can be
taken as usual.
Adapted from:
dcamedical.com
pdf
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Ask about
the use of
medication prescribed by your physician -
If required medications are taken with food, ask for
instructions.
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Avoid
caffeine, sugar, tobacco for one day prior to your exam.
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Avoid rigorous
exercise for one day prior to your exam. |
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Avoid vigorous massage or
muscle manipulations a day or two prior to your exam. |
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Do you have diabetes?
Discuss this with your physician and call the center staff
48 hours before your scan.
For the test to be effective, your blood sugar levels should be be
low.
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Are
you pregnant or
might be?
Generally, PET and PET/CT scans are not performed on
pregnant women.
Adapted from
nps.cardinal.com |
PET Safety?
"Because the radioactivity is very short-lived, your radiation exposure is extremely low. The substance amount is so small that it does not affect the normal processes of the body."
Source: radiologyinfo.org
Radiation
Exposure of Patients Undergoing Whole-Body Dual-Modality 18F-FDG
PET/CT Examinations http://jnm.snmjournals.org/cgi/content/full/46/4/608
Also see Comparing
Imaging for more detail on exposures.
False
Positive PET Results?
"...
"fluorodeoxyglucose (FDG - PET) is not a cancer-specific agent, and false positive findings in benign diseases have been reported in active inflammation or infection, causing false-positive results (1, 2)."
FALSE POSITIVE FINDINGS
"Inflammatory cells such as neutrophil and activated macrophages at the site of inflammation or infection show
increased FDG accumulation (5). Active granulomatous processes, other infectious conditions and active fibrotic
lesions have also been reported to show increased FDG accumulation and cause false-positive PET scans for
malignancy."
1. Goo JM, Im JG, Do KH, Yeo JS, Seo JB, Kim HY, et al. Pulmonary tuberculoma evaluated by means of FDG PET:
findings in 10 cases. Radiology 2000;216:117-121
2. Kostakoglu L, Agress H, Goldsmith SJ. Clinical role of FDG PET in evaluation
of cancer patients. RadioGraphics 2003;23:315-340
source: http://www.kjronline.org/abstract/files/v07n0157.pdf
Think Twice Before Exercising When Getting that PET Scan
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By: Society of Nuclear Medicine | Published: Mar 8, 2006 at 07:01 - yubanet.com/
"Any type of physical activity - from tapping your feet while
in the waiting room to jogging the neighborhood the day before - can
affect the results of a PET scan and lead to false-positive
results," said Medhat M. Osman, M.D., ScM, Ph.D
The study advises technologists to instruct the patients to minimize
muscle activity during the uptake phase and to telephone patients
ahead of their appointments to advise them to refrain from any
excessive muscle activity at least 48 hours before a PET scan.
Brown fat and false positives?
" the phenomenon of 18F-FDG uptake in brown
fat was first discovered when PET/CT fusion images showed 18F-FDG
concentration in the adipose tissue rather than in muscle
or lymph node as previously assumed." http://jnm.snmjournals.org/cgi/content/full/45/1_suppl/72S#F4
SUMMARY by Mozartmom:
"Reasons you might see a light up include
inflammation which could be caused by radiation, chemo, an injury,
or an infection. Thymic rebound (benign activity in the thymus
gland) can cause a light up in the chest. So can brown fat (dense
tissue filled with blood vessels) if you get cold during the scan.
Muscle activity can also cause a light up. Large scar tissue masses
often will have some mild degree of light up. Rarer causes could be
something like even sarcoidosis."
Summary of
potential uses of PET:
GUIDELINES
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PET
Guidelines for Assessment of Response to Lymphoma Treatment CME (2007)
Medscape
(free login required) |
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Studies Assessing
the Utility of PET (in table format)
ncbi.nlm.nih.gov
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"One of the most important skills in PET reporting may be to
recognize its limitations and be clear when a definitive answer
cannot be given to the referring physician's question."
- Barrington, O'Doherty: EJNM 2003:30, suppl. 1: S117-S127
Notes taken from a presentation by
Paul A Hamlin, MD:
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Staging,
such as to verify localized disease?
(experimental; utility varies with subtype of lymphoma)
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Distinguishing
indolent from aggressive histology based on SUV
measurements?
(experimental - not a substitute for pathologic confirmation
from a biopsy)
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Guiding
location of lesion to biopsy?
(could be useful when transformation from indolent to
aggressive is suspected) |
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PET
visualizes follicular lymphoma irrespective of grading.
Ann Oncol. 2006 May;17(5):780-4. Epub 2006 Feb 23.
PMID:
16497824 |
Related
articles |
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Majority
of Transformed Lymphomas Have High SUVs on PET Scanning
Similar To
Diffuse Large B Cell Lymphoma (DLBCL) -
ASH
2006
"... transformation to aggressive lymphoma should be
suspected in patients with indolent
lymphoma found to have high SUVs on FDG PET, and biopsies
should be directed to the
site of greatest PET avidity whenever feasible."
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Predicting
response to treatment early?
(experimental; false positives are possible; probably limited to
curative diseases,
such as DLBCL, Hodgkins)
CLINICAL TRIAL SEARCH:
ClinicalTrials.gov: |
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Evaluating
residual masses following treatment
(common - biopsy may be required if aggressive interventions are
to be used)
"PET is particularly valuable in
delineating viable tumor tissue from areas of tumor
necrosis
or fibrosis after treatment of lymphoma. Because inflammatory
changes after treatment
can create false-positive studies, PET should not be performed
for 3 weeks
after the termination of chemotherapy or 8 to 12 weeks after the
completion of radiotherapy."
Source: http://www.medscape.com/viewarticle/551465 |
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Bone
marrow evaluations?
(sub optimal - MRI is better)
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Follow
up/monitoring?
(limited information, may be useful in select patients with
usual sites of disease) |
Source: Paul A Hamlin, MD -
presentation
Summary of
limitations:
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Some
indolent lymphomas may show only low-grade FDG uptake, |
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FDG
uptake is non-specific (other pathology, inflammations,
infections, HIV, etc), |
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Clinical
limitations of findings
Source: Paul A Hamlin, MD - presentation
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Response to
treatment evaluations?
"Specifically, assessing response
[with PET] may be useful in two possible situations:
(1) to evaluate tumor response at the end of a full course of
treatment, or
(2) to predict tumor response early in the course of a prolonged treatment
regimen [for aggressive lymphomas]. In the first instance, early detection of treatment failure may permit a physician to institute a second-line therapeutic approach.
In the second instance, accurately predicting treatment failure may allow the physician to substitute an alternative regimen, without subjecting the patient to the toxicity of the full course.
" Peter E.
Valk,
MD
TRIAL SEARCH: ClinicalTrials.gov:
Also see PET Scan More Accurate Predictor of
Outcome in [aggressive] Non-Hodgkin’s Lymphoma - cancerconsultants.com
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PET: Every patient is unique:
Individualized therapies for NHL eurekalert.org
PET's ability to identify patients who will respond to
treatments could advance
personalized medicine
"Comparison of PET data on the extent of patients'
disease at relapse and their response
after three months indicated a higher rate of response to the
treatment in patients whose
cancer was limited. In all of the cases, the findings of the PET
scans at three months were
consistent with the clinical findings at six months.
"
... Comment: but did PET reading prior to RIT inform about
response? No.
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But not so fast!
End of
Treatment Evaluations:
"PET is very accurate in
predicting short-term treatment failure. However, it cannot detect
microscopic residual disease and thus its value is hampered by false
negative results in patients relapsing later.
On the other hand, a
biopsy is always indicated before salvage therapy in order to
exclude false positive PET results related to inflammatory lesions
or to second primary tumors." ~ G. H. M.
Jerusalem, et al. - ASCO
presentation
Also see:
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Limitations of PET for
imaging lymphoma. Eur J Nucl Med Mol Imaging.
2003 Jun;30 Suppl
1:S117-27. Epub 2003 May 13. Review. PMID:
12748831
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Predictive value and diagnostic
accuracy of PET treated grade 1 and 2 follicular lymphoma.
Leuk Lymphoma. 2007 Aug;48(8):1548-55. PMID:
17701586
Our results indicate that PET is accurate in the diagnostic
assessment of treated FL-1 and FL-2
and, post-treatment PET positive patients are likely to relapse
prior to PET negative patients.
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PET Standard
Uptake Values (SUV) and proliferation rates in lymphoma?
"FDG uptake in indolent lymphoma appears to be lower than in aggressive lymphomas [17]. Data on the correlation between proliferative activity and glycolysis in malignant tissue, as measured by FDG uptake, are controversial [18, 19]. To date, the correlation between FDG uptake and proliferative activity specifically in indolent lymphoma has not been studied in detail."
Comparison of CT, PET, and PET/CT for Staging of Patients with Indolent Non-Hodgkin’s Lymphoma
pubmedcentral.nih.gov
NOTE: Differences in
administration and tracers across centers may influence SUV
values.
That is, we don't know if the SUV values and reference ranges are
comparable in different centers.
study: FDG-PET Demonstrates Different Metabolic Activities among
Lymphoma Subtypes. abstracts.hematologylibrary.org
Results are summarized in Table 1. The highest mean
SUV’s were obtained in aggressive non-Hodgkin’s lymphomas
(NHL) followed by Hodgkin’s disease (HD) and indolent
NHL.
study:
Majority of
Transformed Lymphomas Have High SUVs on PET Scanning Similar To
Diffuse Large B Cell Lymphoma (DLBCL). Session Type: Poster Session,
Board #580-II
The SUVmax for a transformed aggressive lymphoma ranged
from 3.2 - 30.2,
with a median of 10.8 and mean of 14.
16/28 (57%) patients had an SUVmax above 10; and 12/28
(43%), above 13.
Review article: on PET to determine
grade - Medscape
free login req.
... He concludes that the SUVs are most
helpful in the high and in the low ranges. That is, an SUV > 13
is highly suggestive of an aggressive lymphoma, and an SUV < 6 is
most compatible with an indolent lymphoma. Only 8% of patients with
aggressive lymphoma had SUV < 6, and 6% of patients with indolent
lymphoma had SUV > 13.
However, these upper and lower cutoff values applied to only 55% of
the patients studied. In other words, 45% of the patients had SUV
between 6 and 13. In these, the overlap was sufficient to preclude a
confident assessment of tumor type based on SUV. Using an SUV of 10
as an absolute cutoff results in a 29% misclassification rate for
aggressive NHL and 19% for indolent NHL. This could result in
undertreatment of many patients with aggressive lymphomas and
overtreatment of many with indolent lymphomas."
