This document discusses the benefits and drawbacks of using positron emission tomography (PET) scans to monitor patients who have achieved complete remission from Diffused Large B-cell Lymphoma (DLBCL) after primary treatment. While PET scans can detect relapses early and lead to better outcomes, they also expose patients to radiation and may not be necessary, as the majority of relapses are detected without scans. The document concludes that despite costs and radiation exposure, regular PET scans for two years are important to diagnose the 30% of relapses detected by scans alone and improve prognosis for these patients.

1. Running Head: SURVEILLANCE SCANS IN MONITORING RELAPSES 1
The benefits of surveillance scans in monitoring for relapses in patients who have reached
complete remission after receiving primary therapy for Diffused Large B-cell Lymphoma
Kelly Garcia

2. SURVEILLANCE SCANS IN MONITORING RELAPSES 2
Introduction
The use of positron emission topography scans and computer topography (PET-CT) is
currently standard practice in evaluating patients who have reached complete remission for
Diffused Large B-Cell Lymphoma (henceforth referred to as DLBCL) after primary therapy.
However, the efficiency of PET scans in diagnosing relapses in patients who have gone through
primary treatment of DLBCL and reached complete remission in response to those treatments
has recently been called into question. This paper will seek to analyze the pros and cons of the
use of PET-CT and other surveillance scans in the continuing treatment of DLBCL. After
analyzing the supporting and opposing arguments presented in this paper, it will be clear to the
reader that surveillance scans should be implemented regularly for two years after primary
treatment in patients who are in complete remission for DLBCL. And in addition, surveillance
scans should be covered by insurance and included in health insurance plans fully.
Background
Since the 1990s, PET-CT scans have been invaluable in the initial diagnosis and staging
of hematological diseases- including lymphoma and leukemia. Many physicians also regularly
conduct surveillance scans like PET-CTs in the continuing evaluation of their patients who have
reached complete remission for DLBCL, to watch remission progression and monitor for
possible relapses.
In 2009, approximately 2,000 PET-CT machines were installed in the United States
(Buck et al., 2010). This number reflects the growing popularity of PET-CT scans as tools of
monitoring and diagnosing. Despite the diagnostic and prognostic benefits of surveillance PET-
CT scans in this role, some insurance companies do not cover regular-interval surveillance scans.

3. SURVEILLANCE SCANS IN MONITORING RELAPSES 3
They may only cover them partially, or in some cases not at all. As a result, patients are forced to
choose between paying out of pocket, and risk relapse by not utilizing these early detection tools.
Definitions for the rhetoric included in this paper will now be clarified. According to the
Leukemia and Lymphoma Society, lymphoma is the name for a group of blood cancers that
develop from the lymphatic system. This means they affect the immune and blood systems- and
consequently are commonly referred to as blood cancers. They are categorized into two main
groups, Hodgkin lymphoma and Non-Hodgkin lymphoma. According to the Dana-Farber Caner
Institute, Hodgkin lymphoma is distinguished by the presence of Reed-Sternberg cells, mature B
cells that have become malignant (2015). Reed-Sternberg cells are unusually larger, and tend to
carry more than one nucleus. Non-Hodgkin lymphoma is a heterogeneous collection of
lymphomas that differ in some way from the classic manifestation of Hodgkin lymphoma. This
group is by far the more numerous of the two. Diffused Large B-cell lymphoma (DLBCL) is an
aggressive cancer that accounts for 30-40% of all Non-Hodgkin lymphomas (Dabaja et al.,
2013). After primary treatment of any cancer, a patient may go into complete remission, which is
the absence of any disease completely. A relapse may occur after a patient has reached complete
remission through some line of therapy. Recurrence refers to the continuation of disease after
only a partial response. Because of this distinction, most physicians agree that recurrences are a
result of disease that is not completely eradicated, and relapses are a new development of
disease. Because this paper focuses on PET-CT scans used as evaluation methods for patients
who reached CR after the use of primary treatment, the focus will be on the risk of relapse in
patients who have received first line treatment for DLBCL, and gone into complete remission as
a response.
Supporting Arguments

4. SURVEILLANCE SCANS IN MONITORING RELAPSES 4
Risk of Relapse
Firstly, there is a significant risk of relapse in patients who have received primary
treatment for DLBCL. The risk for relapse is particularly high soon after primary treatment, with
two-thirds of relapses occurring within the first 18 months after treatment (Cheah et al., 2013). In
addition, 85% of relapses occur within the first two years after treatment (Cheah et al., 2013). Of
all patients who have received first line treatment for DLBCL, a total of 30% of patients
experience a recurrence/relapse after primary treatment (Petrausch et al., 2009). Certain
prognostic factors determine whether the rate for relapse is high in particular patients. Relapse is
particularly prevalent in patients who had an initial International Prognostic Index (IPI) above 3
(Cheah et al., 2013). The International Prognostic Index takes into account factors such as age,
stage of disease at diagnosis, LDH blood serum levels, and number of extranodal sites to assign a
number, that reflect the expected prognosis of the patient (Oncology Pro, 2008). Because
relapses are fairly common with DLBCL, it is critical that surveillance scans be conducted in
patients who are in remission to detect relapse early.
High Accuracy of PET-CT
Furthermore, if and when DLBCL relapses, PET-CT scans as surveillance scans have a
relatively high rate of true positives and true negatives, called sensitivity and specificity
(respectively) (Bouthaina et al., 2013). The studies that show PET-CT sensitivity measure it to
be upwards of 100% (Bouthaina et al., 2013). The studies that show PET-CT specificity measure
it to be somewhere between 67-100% (Bouthaina et al., 2013). These numbers reflect how
accurate PET-CT scans are in showing the true state of disease. Because surveillance tests causes
stress, and stress can exasperate or even cause sickness (American Psychological Association,

5. SURVEILLANCE SCANS IN MONITORING RELAPSES 5
2013), it is critical that surveillance scans be as accurate as possible. Because the sensitivity and
specificity of PET-CT scans provide fairly accurate results, stress is minimized for patients.
Better Prognostic Outcomes
When a relapse is diagnosed by subclinical, asymptomatic means, the prognostic outlook
for the patient is more positive (Liedtke, Hamlin, Moskowitz, & Zelenetz, 2006). In patients who
are diagnosed subclinically, the scope of disease is smaller and therefore has a higher chance of
being eradicated by second line therapy. Liedtke et al. (2006), found that patients were about
four times more likely to have a low-risk disease if their relapse was diagnosed through PET-CT
(as opposed as being diagnosed by symptoms). According to the same study, they were also
more likely to have a chemosensitive (one that responds well to chemotherapy) disease than
symptomatic patients, which is a positive prognostic factor.
Zinzani et al. (2009) note that, logically, it is useful to detect a relapse as early as possible
in order to increase the possibility of obtaining remission. In a study conducted by Liedtke et al.
(2006), those who were diagnosed by a scan had a longer average progression free survival of 34
months (as compared to 11 months in the symptomatic patients). In addition, the same study
found the median overall survival rates at five years of those whose relapse was diagnosed by
routine imaging as opposed to those diagnosed by symptoms were 54% and 43%, respectively.
Opposing Arguments
Radiation Exposure
Firstly, critics argue that the use of PET-CT scans as surveillance expose patients to
unnecessary radiation. Ionizing radiation has been associated with carcinogenic risk (Nievelstein
et al., 2012). This is due to the ionization of water molecules in the body, which can cause DNA
strand breaks or base damage (Lin, 2010). And although the body normally fixes these

6. SURVEILLANCE SCANS IN MONITORING RELAPSES 6
abnormalities, they can also lead to point mutations, chromosome translocations, and gene
fusions that may lead to cancer (Lin, 2010). Even worse, is the long incubation time between
radiation exposure and cancer diagnosis, at least five years, but sometimes between 10 and 20
years (Lin, 2010). This longer incubation time puts young people more at risk for development
of a secondary malignancy if they receive regular PET-CT scans.
The radiation dose given during scans varies for each person based on weight, but on
average, an abdominal CT may be around 10mSv (millisieverts) (Lin, 2010). In comparison, the
yearly average radiation exposure is 3mSv, mainly from radon gas in the home (Lin, 2010).
There is no data that supports that any radiation exposure below 100mSv carries an increased
rate of cancers (Lin, 2010). Due to this threshold of 100mSv, PET-CT scans pose little risk to the
development of radiation-caused cancers when used responsibly, even in younger patients.
Watchful Waiting
Finally, in practice, less than 50% of DLBCL relapses are caught through scheduled,
routine PET-CT. In fact, less than one-third of recurrences are detected at an asymptomatic stage
(Zhang et al., 2015). Further, in a study by Cheah et al. (2013), in their cohort 83-89% of
relapses are detected through a practice called ‘watchful waiting’. Watchful waiting is a common
practice with indolent lymphomas that waits for the presentation of symptoms before starting
treatment (National Institute of Health, n.d.). A patient who is being monitored in this way would
have regular doctor’s appointments and blood tests to watch for signs of relapse. These signs
might include evaluated LDH levels, examination findings (swollen lymph nodes), fever, or
collapse. In the Cheah et al. (2013) study, 54% of patients who experienced a relapse were
diagnosed through abnormal blood results.

7. SURVEILLANCE SCANS IN MONITORING RELAPSES 7
Of course, when using PET-CT as surveillance scans, a patient is also regularly seeing
their oncologist and undergoing blood tests. In this way, PET-CT surveillance scans can be
combined with watchful waiting to be part of a holistic and effective treatment plan.
Burden of Cost
Because PET-CT scans only detect approximately 30% of relapsed DLBCL, the majority
of cases are not caught by PET-CT scan. Additionally, the cost of PET-CT scans is relatively
high because it is newer technology. For example, Medicare only covers up to three PET-CT
scans after the end of initial treatment for cancer and any subsequent scans must be approved
(Berger & Schuester, 2014). Approval will be given if there is an indication of disease or relapse
is suspected; however, in asymptomatic patients who are using PET-CT as part of their treatment
plan, the imposed limit is upheld (Berger & Schuester, 2014). If a patient’s insurance does not
cover routine scans, then the patient is left to make the decision about whether they want to pay
out of pocket. It could be argued that watchful waiting is more cost-effective. The average cost
of a single PET-CT is $2,138USD (El-Galaly et al., 2010). According to the same study, over the
recommended course of two years, this would be $10,522USD; including regular doctors visits
and blood tests. In comparison, a quarterly blood test costs $31USD and a doctor’s appointment
costs $219USD (El-Galaly et al., 2010).
Doctors will order PET-CT scans as medically necessary and patients will want to use
them because these surveillance tests can reach remission before symptoms occur and provide
better prognostic outcomes. If insurance companies do not allow medically necessary
surveillance, economically disadvantaged patients will feel the impact more severely. In light of
these numbers, patients may choose to forego the surveillance scans to keep costs low, especially
if their insurance does not cover them.

8. SURVEILLANCE SCANS IN MONITORING RELAPSES 8
Conclusion
Although surveillance scans are standard continuing treatment in patients in
remission for DLBCL, some research has suggested that PET scans may not be the way that
most relapses are detected, and cause unnecessary financial costs and radiation exposure.
However, the same and other research indicates that when relapse is detected through PET-CT,
there is a significantly better prognostic outlook. If physicians were to stop using PET scans as
surveillance methods, instead relying solely on physical examinations and blood levels, a
significant number of patients whose relapse is diagnosed through PET-CT scans (30% of those
who relapse) would not be diagnosed until after the disease becomes symptomatic. As shown
by research cited in this paper, these individuals would have a significantly more negative
prognostic outcome and lower rates of cure.
While there is some merit to the argument that PET-CT scans do not detect the majority
of relapsed DLBCL cancers and that the costs and radiation exposure are significant, this
argument is outweighed by the significant benefits available when cancer relapse is diagnosed
before symptoms occur. Therefore, receiving regular PET exams for the first two years after
reaching complete remission for DLBCL is necessary to increase prognostic outcomes. In
addition, these scans should be covered completely by insurance companies.

9. SURVEILLANCE SCANS IN MONITORING RELAPSES 9
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