The medical community and oncologists in particular have
enthusiastically embraced the use of PET scans, or more recently, scans
combining both PET and computerized axial tomography. The adoption of the PET
scan has been most notable in the treatment of lymphomas where its
incorporation into the care of Hodgkins and non-Hodgkins lymphomas
is now virtually universal. PET scans have clearly impacted the way lymphomas
are staged and treated, particularly those types with the potential for cure,
such as classical Hodgkins lymphoma and large cell and/or aggressive
lymphoma. PET scans have also engendered some rethinking of our care of these
PET scans, because of their enhanced sensitivity and
convenience, have almost totally replaced gallium scans. Unlike gallium scans,
PET scans are routinely used in staging since the scans are able to reveal
disease in normal sized lymph nodes (on CT scan) which would otherwise have
been interpreted as unremarkable.
PET scanning has altered treatment approaches as well.
For instance, bulky masses, despite being sterilized of lymphoma, are often
characterized by some residual mass or scar. Using conventional means, it has
been difficult to determine whether the residual mass after treatment did or
did not contain active disease. As a result, these masses had been routinely
irradiated even if a biopsy showed scar (because of possible sampling error).
Although many still advocate irradiating bulky masses, the advent of the PET
scan has engendered a rethinking of this approach when no disease activity is
Today, a truly negative PET scan at the completion of
therapy has become the sine qua non for a complete remission. Few relapses
occur, usually in singledigit percentages. Data are also emerging that
determination of a response early, after one, two or three cycles of
chemotherapy, may be even more predictive of outcome for classical
Hodgkins lymphoma and large cell lymphoma than that obtained at the end
of therapy. This has prompted the initiation of trials to determine whether
altering therapy early, based on interim PET scanning, may be beneficial.
Data show that a positive PET scan obtained during or
after chemotherapy predicts for a high probability of treatment failure. If
that is true, should a positive PET scan obtained after interim chemotherapy,
mandate alternative therapy be immediately pursued, particularly if the results
are substantiated by biopsy? Would this spare unnecessary, ineffective therapy
and/or would the initiation of different measures, for example,
transplantation, still rescue the patient? It is possible that a strongly
positive PET scan may simply be a doleful predictor of drug resistance, which
may not be overridden by the exponential doses of chemotherapy
given in transplantation.
In the presence of an early interim negative PET scan,
can therapy be shortened, since by convention, chemotherapy is given two cycles
beyond complete remission? Treatment could then be stopped after three, four or
five cycles of chemotherapy rather than the conventional six. If very few
relapses occur after a negative PET scan, is there a need for serial follow-up
scans because the likelihood of relapse would be small? There are no compelling
data to indicate that a somewhat earlier detection of relapse by PET in these
rare relapsing patients would alter subsequent therapy or ultimate outcome.
Would the yield outweigh the cost, anxiety and radiation associated with serial
The role of PET scans in low-grade lymphoma is less
clear. In general, but not always, the semiquantitative standard uptake value
(SUV) scores for low-grade lymphoma are low, usually seven or less, whereas
those for large cell and/or aggressive lymphoma is twelve or higher. Scores
between seven and twelve represent an intermediate zone and may often be seen
with classical Hodgkins lymphoma. If a higher than expected SUV score in
a node or nodal area in an apparent low-grade lymphoma is discovered, it should
prompt and direct a biopsy to the area for the presence of aggressive disease.
This is particularly useful at initial diagnosis where more than one type of
lymphoma pathology may be present or later when transformation is suspected.
This utility, however, does not warrant the routine, serial follow-up of
low-grade lymphoma by PET scan.
Having described the exciting, brave new world of PET
scans in lymphoma, words of caution are in order. All is not rosy. For
starters, it isnt always clear what constitutes a positive or negative
study. Is the eyeball assessment more accurate than the semiquantitative SUV
scores? If SUV scores are used, what low level of SUV activity represents
negativity? What background determinants are being used? Further, data amongst
machines are not readily transferable. The interval between injection of the
radioisotope and subsequent measurement has been variable, not fully
standardized, and can affect results. Conditions other than lymphoma may result
in a positive PET scan and include infection, thymic rebound, late infiltration
of inflammatory cells and/or post-therapy changes.
Perhaps most distressing are the preliminary reports of discordance
among observers independently reviewing the same scans. This discordance is
reminiscent of the discordance among lymphoma pathologists rendering
independent reviews of the same slides. When the material is clear-cut, as with
follicular lymphoma in pathology, an unequivocal negative or positive PET scan
can be easily diagnosed and yield a high degree of concordance among reviewers.
It is the subtle or gray areas that create difficulty. For instance, PET scans
showing a major but not complete fall in the SUV scores can create difficulties
in interpretation. Despite difficulties with subtleties, no one
would suggest discarding the use of PET scans any more than one would suggest
discarding subclassifying lymphomas. PET scans are here to stay and clearly
represent a major advance in the care of lymphoma.
Morton Coleman, MD, is Director of the Center for
Myeloma and Lymphoma at Weill Cornell Medical College and the Section Editor of
the Hematologic Malignancies section of the HemOnc Today Editorial Board.