Standard Uptake Value Predicts Survival in Non–
Small Cell Lung Cancer
Ikenna C. Okereke, MD, Sidhu P. Gangadharan, MD, Michael S. Kent, MD,
Saila P. Nicotera, MD, Changyu Shen, PhD, and Malcolm M. DeCamp, MD
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and Division of Biostatistics,
Indiana University School of Medicine, Indianapolis, Indiana
Background. Integrated [18F]fluorodeoxyglucose positron
emission tomography– computed tomography (PET-CT)
scan is a widely used modality in the evaluation of lung
cancer. Our goal was to determine the ability of the stan-
dard uptake value (SUV) of the primary tumor (SUV-T) and
regional lymph nodes (SUV-N) to predict survival.
Methods. From January 2005 through June 2007, 584
consecutive patients undergoing integrated PET-CT scan
for suspected lung cancer were studied. Results of inte-
grated PET-CT scans, including the maximum SUV-T
and SUV-N, were recorded. A patient was defined as
having a positive PET scan if the maximum SUV (T or N)
was greater than 2.5. Overall survival was documented
from clinical records and the Social Security Death Index.
Cox regression analysis was used to evaluate the corre-
lation between SUV and survival.
Results. Among patients with a positive PET scan (n ⴝ
L ung cancer is the most lethal malignancy in this coun-
try, with up to 160,000 deaths per year [1] attributable
to this disease. As such, the ability to diagnose and treat
lung cancer remains a major public health concern.
Positron emission tomography– computed tomography
(PET-CT) scan, which is widely used in the management of
lung cancer, has become an important diagnostic modality
in the process of evaluating and staging patients appropri-
ately. The PET scan, which measures the uptake and
trapping of radiolabeled glucose by tissues [2], assists in
determining the presence of locoregional and metastatic
disease. The extent of disease detected by PET-CT scan
could impact the decision to operate and guide the need for
adjuvant or neoadjuvant therapy.
The results of PET-CT scan may also be able to stratify
patients with lung cancer in terms of ultimate prognosis,
as has been shown in previous studies [3– 6]. Our goals
were to determine whether the clinical stage, based on
preoperative PET-CT scan, predicts overall outcome and
to understand the correlation between standardized up-
take value (SUV) and survival.
Accepted for publication May 28, 2009.
Presented at the Forty-fifth Annual Meeting of The Society of Thoracic
Surgeons, San Francisco, CA, Jan 26 –28, 2009.
Address correspondence to Dr Okereke, Department of Surgery, Section
of Cardiothoracic Surgery, Indiana University School of Medicine, 545
Barnhill Dr, EH 215, Indianapolis, IN 46202; e-mail: iokereke@iupui.edu.
© 2009 by The Society of Thoracic Surgeons
Published by Elsevier Inc
GENERAL THORACIC
329), both SUV-T and SUV-N were predictors of survival.
As maximum SUV of the primary mass increased, sur-
vival decreased (hazard ratio, 1.05; p < 0.001). As maxi-
mum SUV of locoregional lymph nodes increased, sur-
vival also decreased (hazard ratio, 1.06; p < 0.001).
Furthermore, among patients with no mediastinal dis-
ease identified by PET-CT scan, increased SUV-T contin-
ued to predict poor survival (hazard ratio, 1.06; p ⴝ 0.001).
Conclusions. Local and regional maximum SUVs de-
fined by integrated PET-CT scanning have a strong
correlation with survival in patients with non–small cell
lung cancer. An elevated SUV is known preoperatively
and may assist clinicians in stratifying patients at in-
creased overall risk preoperatively.
(Ann Thorac Surg 2009;88:911– 6)
© 2009 by The Society of Thoracic Surgeons
Material and Methods
Patients
From January 2005 through June 2007, 584 consecutive
patients undergoing integrated PET-CT scan for sus-
pected non–small cell lung cancer were studied, regard-
less of whether they ultimately underwent surgery. Pa-
tients who were determined to have small cell lung
cancer were excluded from the study. Approval from the
institutional review board was obtained. Qualitative and
quantitative results of integrated PET-CT scans, includ-
ing the maximum SUV [7] of the primary mass (SUV-T)
and regional lymph nodes (SUV-N), were recorded. A
patient was defined as having a positive PET scan if the
maximum SUV (T or N) was greater than 2.5 [8]. Overall
survival was documented from clinical records and the
Social Security Death Index. Cox regression analysis,
Kaplan-Meier analysis, and the log-rank test were used
to evaluate the correlation between SUV and survival.
Outcomes
The results of the integrated PET-CT scan, including
SUV-T and SUV-N, mass size, presence of lymphade-
nopathy by CT criteria (⬎1 cm in short-axis dimension),
and location of positivity were recorded. Similarly, the
clinical and pathologic stages were determined, using
standard TNM classifications [9], in patients who under-
went surgery. Survival data was obtained through elec-
0003-4975/09/$36.00
doi:10.1016/j.athoracsur.2009.05.083
 912 OKEREKE ET AL Ann Thorac Surg
STANDARD UPTAKE VALUE AND SURVIVAL IN NSCLC 2009;88:911– 6

Table 1. Demographics When evaluating a mass or a lymph node, the maximum

SUV within the structure was used. The highest SUV of
Patients 584
any lymph node was used to represent SUV-N.
Age (y), mean 67 ⫾ 0.5
Male 47% Statistical Analysis
ECOG ⱖ2 16%
Continuous variables were summarized by mean and
Smoking, current 20% standard error, and categorical variables were summa-
Pack-years 54 ⫾ 2.6 rized by frequency and percentage. Cox proportional
Smoking, past 59% hazard model was used to correlate continuous indepen-
Pack-years 46 ⫾ 1.8 dent variables with survival. The association between
Smoking, never 21% SUV and mortality for individual stage or grouping of
ECOG ⫽ Eastern Cooperative Oncology Group.
stages was analyzed in combination with a Cox regres-
GENERAL THORACIC

sion model, controlling for mass size and largest node

tronic medical records and verified using the Social
Security Death Index.
Surgical procedures were performed by 3 staff sur-
geons at the Beth Israel Deaconess Medical Center. Each
surgical procedure was performed using either video-
assisted thoracoscopic surgery or an open approach,
depending on patient and tumor characteristics. Preop-
erative staging of the mediastinum was performed using
esophageal ultrasound and endobronchial ultrasound
when deemed appropriate. Mediastinal lymph node
sampling and dissection were performed routinely as a
part of the procedure.
Positron Emission Tomography–Computed
Tomography Scan
All patients fasted for greater than 4 hours before the
scan. Blood glucose levels were determined before ad-
ministration of 10 Ci [18F]fluorodeoxyglucose (18FDG).
Sixty minutes after administration of 18FDG, PET and CT
scans were obtained from the skull base to the level of the
hips. All integrated PET-CT scans were reviewed by
radiologists who specialized in nuclear medicine tech-
niques. A PET-CT scan was interpreted as positive if the
maximum SUV-T or SUV-N of a study exceeded 2.5.
Images obtained from PET scan were reconstructed
using standard algorithms. Abnormal 18FDG uptake was
defined as areas with activity greater than in surrounding
tissue and unrelated to sites with normally increased
uptake of tracer (myocardium) or excretion (bladder). For
the calculation of SUV, circular regions of interest (ⱖ70
pixels) were drawn on axial images adjacent to areas of
increased 18FDG uptake. The SUV was calculated using
the following equation:
SUV ⫽
decay ⫺ corrected activity 关kBq兴 ⁄ tissue volume 关mL兴
injected ⫺ 18FDG activity 关kBq兴 ⁄ body weight 关g兴
size. The proportional hazard assumption was tested by
the approach proposed by Lin and colleagues [10]. Sur-
vival functions of different populations were estimated
by Kaplan-Meier estimator and compared by log-rank
test. All analyses were performed by SAS 9.1 (SAS
Institute Inc, Cary, NC).
Results
Demographics
The study included 584 patients. Table 1 lists the demo-
graphics of the patient population. Average age was 67
years. Tissue diagnosis was obtained in 417 patients
(71%). Ultimately, 246 patients underwent mediastinos-
copy or surgical resection.
Accuracy
Positron emission tomography– computed tomography
scan results are listed in Table 2. A PET stage of III or
higher was assigned to 36% of patients. The PET-CT scan
was positive in the mediastinum in 164 patients (28%).
When comparing pathologic data with PET-CT results in
patients who underwent mediastinoscopy or surgical
resection, the sensitivity and specificity of PET-CT scan
were 87% and 43%, respectively.
Survival
Figure 1 shows survival stratified by PET stage. There
was a statistically significantly correlation between PET
stage and survival (p ⬍ 0.001), with survival decreasing as
PET stage increased.
Standardized Uptake Value
The correlation between SUV and survival was exam-
ined. Patients with M1 disease identified by PET scan
were excluded from analysis. All other patients were
included. Table 3 shows the SUV levels for each PET

Table 2. Positron Emission Tomography–Computed Tomography Scan Results

Variable PET Stage 0 PET Stage I PET Stage II PET Stage III PET Stage IV

N 170 169 35 122 88

Mass size, mean (cm) 1.5 ⫾ 0.1 2.3 ⫾ 0.1 2.7 ⫾ 0.3 3.2 ⫾ 0.2 3.5 ⫾ 0.2
Mass SUV, mean ... 7.3 ⫾ 0.4 10.8 ⫾ 1.4 12.1 ⫾ 0.6 11.7 ⫾ 0.8
Attempt at tissue procurement 36% 83% 86% 86% 91%

PET ⫽ positron emission tomography; SUV ⫽ standardized uptake value.

Ann Thorac Surg OKEREKE ET AL 913
2009;88:911– 6 STANDARD UPTAKE VALUE AND SURVIVAL IN NSCLC

GENERAL THORACIC
Fig 1. Positron emission tomography (PET) stage versus survival. Fig 2. Standardized uptake value of the primary mass (SUV-T) ver-
sus survival.

stage. As the SUV-T increased, overall survival decreased

(hazard ratio, 1.05; p ⬍ 0.001). Similarly, as the SUV-N
increased, survival diminished (hazard ratio, 1.06; p ⬍
0.001).
Although SUV is a continuous variable, we thought
that establishing “high-risk” and “low-risk” groups,
based on SUV values, would act as a useful reference for
clinicians. Dichotomization of SUV values was based on
the 75th percentile values and, once again, included only
patients in PET stages I, II, and III. Patients who had an
SUV-T higher than 12.5 had worse survival than patients
with an SUV-T less than 12.5 (p ⬍ 0.001; Fig 2). Similarly,
patients with an SUV-N higher than 9.7 had worse
survival than patients with an SUV-N less than 9.7 (p ⫽
0.046; Fig 3).
The correlation of SUV-T with survival was next exam-
ined in each individual stage. Results are shown in Table
4. The association of SUV-T with mortality was most
pronounced for patients in PET stage II, and was signif-
icant for PET stages I and II combined and PET stages I,
II, and III combined. These associations were indepen-
dent of mass size and largest node size.
group of patients with no mediastinal disease identified
by PET-CT scan, as SUV-T rose, survival diminished
(hazard ratio, 1.06; p ⬍ 0.001). Furthermore, patients were
divided into “high-risk” and “low-risk” groups based on
75th percentile values of SUV-T. In patients with a
negative mediastinum, an SUV-T of 10 was identified as
a cutoff for survival (p ⫽ 0.05; Fig 4).
Malignant Disease
Pathologic evidence of malignancy, diagnosed by medi-
astinoscopy, surgical resection, or fine needle aspiration
(FNA), was reported in 266 patients (46%). After exclud-
ing M1 disease, 232 patients remained. In this group of
patients, there was still a significant correlation between
SUV-T and survival (hazard ratio, 1.04; p ⫽ 0.03). There

Mediastinum-Negative
Clinical stage I or II disease was found in190 patients
(58%) on the basis of their PET-CT scans. Among this

Table 3. Standardized Uptake Value Levels

PET Stage N SUV-T (mean) SUV-N (mean)

0 170 ... ...

I 169 7.3 ...
II 35 10.8 4.8
III 121 12.1 7.7
IV 89 11.7 10.6

PET ⫽ positron emission tomography; SUV-N ⫽ standardized uptake

value of the regional lymph nodes; SUV-T ⫽ standardized uptake Fig 3. Standardized uptake value of the regional lymph nodes
value of the primary mass. (SUV-N) versus survival.
 914 OKEREKE ET AL Ann Thorac Surg
STANDARD UPTAKE VALUE AND SURVIVAL IN NSCLC 2009;88:911– 6

Table 4. Standardized Uptake Value Versus Survival in Each Stage

Unadjusted Adjusteda

PET Stage Hazard Ratio p Value Confidence Interval Hazard Ratio p Value Confidence Interval

I, II, III 1.05 ⬍0.001 1.03–1.08 1.04 0.003 1.01–1.07

I, II 1.05 0.002 1.02–1.09 1.05 0.01 1.01–1.09
I 1.03 0.26 0.98–1.08 1.02 0.44 0.97–1.07
II 1.17 0.001 1.07–1.28 1.20 0.001 1.07–1.34
III 1.03 0.17 0.99–1.09 1.03 0.34 0.97–1.08
a
Adjusted for mass size and largest node size.

PET ⫽ positron emission tomography.

GENERAL THORACIC

was also a significant correlation between SUV-N and value, with values above 2.5 considered positive and
survival (hazard ratio, 1.11; p ⫽ 0.01). values below 2.5 considered negative. The results of this
study argue that SUV should instead be used as a
gradient, and higher values should potentially alter over-
Comment
all treatment plan. Decisions about whether to perform
The goal of our study was to understand the ability of mediastinoscopy before resection [12], the need for adju-
PET-CT scan to predict overall outcome. Our results vant therapy [13], and the frequency of postoperative
show that PET-CT scan can in fact act as a prognosticator surveillance all may be affected by preoperative SUV
for long-term survival. There are many different aspects levels.
of PET-CT scan that were reviewed in this study. Our study has shown that survival decreases as SUV of
Overall PET stage was seen to predict survival in our the primary tumor or locoregional lymph nodes in-
study. This finding has been seen previously [4] and is in creases. An important point that remains to be discov-
part related to the poor overall outcome in patients ered, however, is the mechanism of failure in these
identified with advanced disease, especially in patients patients. One potential mechanism is that tumors with
with M1 disease [11]. higher SUV values have a more advanced stage at
Because patients with M1 disease have such guarded surgery than predicted by the preoperative PET stage,
outcomes, we performed separate analyses of the role of implying that as the SUV increases, accuracy decreases.
SUV versus survival excluding these patients. Even after Another potential mechanism is earlier local recurrence
excluding patients with M1 disease, there was still a of disease, implying that tumors with higher SUV values
significant correlation between SUV and survival, both in are more locally aggressive. Yet another possible mech-
the primary tumor and in locoregional lymph nodes. This anism is an increased propensity for distant metastasis.
correlation was also significant in the group of patients Prospective studies are required to determine the abso-
with pathologic evidence of malignant disease. Impor-
tantly, these analyses were performed adjusting for mass
size to prevent potential confounding from a variable
already known to be associated with worse survival.
These findings are important in that they can perhaps
guide treatment plan based on these values, as the SUV
levels are known preoperatively.
We also thought it was important to analyze the
correlation of SUV with survival within each clinical
stage. Although the only individual stage with a statisti-
cally significant association of SUV and survival was for
patients with PET stage II, the group of patients with no
clinical evidence of disease in the mediastinum (PET
stages I and II) and the group of patients with no clinical
evidence of metastatic disease (PET stages I, II, and III)
each had significant associations. These two groups are
composed of the patients most likely to benefit from
appropriate preoperative risk stratification and potential
surgical resection. Whereas the long-term survival in
patients identified with M1 disease is unlikely to be
affected considerably, alterations in management based
on SUV can potentially impact long-term outcome in
patients with stage I, II, or III disease identified clinically. Fig 4. Survival in mediastinum-negative patients. (SUV ⫽ stan-
Many centers now use SUV primarily as an “all or none” dardized uptake value.)
Ann Thorac Surg
2009;88:911– 6
lute causes for decreased survival in patients with higher
SUV values.
Although we believe that SUV should be used as a
gradient, we attempted to find a cutoff value, above and
below which there were significant differences in sur-
vival. We were able to achieve this both for SUV-T and
SUV-N, with values of 12.5 and 9.7, respectively. We
believe that these cutoff points can be useful as a refer-
ence for clinicians, and may eventually be able to be
incorporated into a staging system. Further prospective
studies are required, however, before this goal can be
achieved. This cutoff would be especially practical in
patients with no evidence of mediastinal disease preop-
eratively. Better ability to stratify these patients would
lead to more accurate prediction of long-term outcome
and more appropriate treatment preoperatively. Our
results argue that patients with a high SUV would po-
tentially profit from a more aggressive treatment plan,
including mediastinoscopy before resection of the pri-
mary tumor and adjuvant chemotherapy, regardless of
final pathologic results.
The goals of this study were to determine the ability of
PET-CT to predict survival in patients with suspected
lung cancer, and to understand which specific aspects of
PET-CT were important. Preoperative PET stage does
predict long-term outcome, and SUV values predict sur-
vival. Further studies are required to determine mecha-
nisms of failure related to higher SUV values.
References
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DISCUSSION
DR DAVID R. JONES (Charlottesville, VA): I had two quick
questions for you. How many patients had bronchioloalveolar
cell carcinoma given that they typically have a low SUV (stan-
dardized uptake value) value? What do you think if you ex-
cluded those, would it have any impact on your analysis?
Second, what do we do now with the patient who is medias-
tinoscopy negative, but who has a tumor with an SUV of 15 and
a node of 12, which would fall into your high-risk group? Should
we give those patients induction chemo? Is your group starting
to look at that or considering it?
DR OKEREKE: I think those are both great questions. I think the
second one goes toward the heart of the relevance of this study.
To answer the first question, approximately 10% to 15% of our
patients had bronchoalveolar pathology. As such, I would say
that bronchoalveolar probably does not have a significant im-
pact toward the overall results of this study. This is my
approximation.
As to the second question, I think that once again the rele-
vance of this study is, especially in mediastinal-negative patients
with a very high SUV, should we do neoadjuvant strategies? I
think based on this, the next study should be a prospective
randomized trial looking at SUV and potentially separating
patients into two groups, one with neoadjuvant and one without.
I think that will be the next step.
OKEREKE ET AL 915
STANDARD UPTAKE VALUE AND SURVIVAL IN NSCLC
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DR MICHAEL J. LIPTAY (Chicago, IL): I enjoyed the paper very
much. I have a question along similar lines when the tumor SUV
is high and the hilar and mediastinal nodes are negative. Do you
change your strategy at all?
Secondly, did you find in the pathologic analysis of the
surgical specimens that the nodes had a higher incidence of
being positive; that is, high SUV in the tumor may predict nodal
positivity because it’s a more aggressive tumor?
DR OKEREKE: Yes, that’s a great question. In fact, that’s what
we investigated. It did not specifically say, and there was no
statistical significance in the difference of concordance between
the two in that situation. But I think that’s what potentially
further analysis would need to consider.
DR JOSHUA R. SONETT (New York, NY): Excellent presenta-
tion. Did you look at all at the size of the tumor relative to the
SUV and quantitate SUV for the size?
So does a 1-cm tumor that throws off an SUV of 10 versus a
10-cm tumor that throws off an SUV of 10 have different clinical
outcomes, as per gram of tumor the smaller tumor appears more
active?
DR OKEREKE: Yes, we did. Yes, I didn’t include that. The size
of the tumor was correlated with survival, which is not too
 916 OKEREKE ET AL
STANDARD UPTAKE VALUE AND SURVIVAL IN NSCLC
unexpected. Secondly, these results were independent of mass
size.
DR LIPTAY: No. But did you ever think of dividing by the size
of the tumor, so an SUV, like a Dlco (lung diffusing capacity for
carbon monoxide), for the size of that tumor?
DR OKEREKE: Oh, I see. No, we did not.
DR LIPTAY: So a 1-cm tumor that throws off an SUV of 5 may
be worse than a 5-cm tumor that throws off an SUV of 12. It may
bespeak early to the bad biologic character of it, but it didn’t get
big enough to throw off an SUV of 12.
GENERAL THORACIC
DR OKEREKE: No, I think that’s a good point.
DR LIPTAY: But you have that data, so it might be nice for us to
see it in the future.
DR PAUL DE LEYN (Leuven, Belgium): Thank you for your very
nice presentation. As you know, SUV is not at all standardized.
It might be standardized in one institution for one PET (positron
emission tomography) scanner, but you cannot transmit the data
for other PET scanners.
Can we use the data from your center to select patients for
adjuvant therapy in centers with other PET scanners?
DR OKEREKE: Yes. Though it is called Standard Update Value,
it’s quite nonstandard across different PET scanners.
We eliminated that problem at our institution because we had
a single PET-CT scanner which was used for all 584 patients. But
I think trying to apply a cutoff value among different institutions
may have some degree of difference.
That being said, there has been some work by Dr Cerfolio.
That’s one of the papers that we’ve referenced. His cutoff value
by a different methodology was about 10. We had a cutoff value
for the primary tumor of 12.5.
I think that there will be some gray area, but it still should not
eliminate the possibility of trying to create some type of ran-
domized trial looking at neoadjuvant strategies based on SUV. I
think that’s a great point, though.
DR SETH D. FORCE (Atlanta, GA): I have a quick question. I
think that one of the previous questions may have addressed
this, but I didn’t see kind of a report of the accuracy of your PET
Ann Thorac Surg
2009;88:911– 6
imaging. And so for patients who were N1 positive by PET, what
was the concordance in pathologic specimens?
DR OKEREKE: Right. N1 disease was very limited preopera-
tively, but I think it’s a good point.
DR JONES: Did you do a multivariate analysis of SUVmax?
You’re saying it’s a marker of a poor prognosis if it’s above or
below a certain number. But is it an independent predictor of a
poor prognosis?
Did you look at tumor size, pathologic stage, or other kinds of
histopathologic variables such as grade or lymphovascular
invasion?
DR OKEREKE: To answer your question, yes and no. We did it
based on mass size as well.
DR JONES: And was it a multivariate analysis?
DR OKEREKE: Yes.
DR LEDFORD POWELL (Newport Beach, CA): A quick ques-
tion. I enjoyed the presentation. You actually answered a lot of
questions that I had had about PET scans previously.
I did want to know whether or not you noticed a correlation
between the mediastinal-negative patients that had high pri-
mary tumor SUVs and their tumor biology, meaning if they had
a low SUV, did they have moderately differentiated adenocarci-
noma? And if they had a higher SUV, did they have a more
aggressive tumor?
And should we be considering the aggressiveness of the
tumor when we’re looking at whether or not these patients need
to get chemotherapy?
DR OKEREKE: Yes, I think potentially, and, no, we did not
notice that.
DR JEAN-FRANCOIS LEVI (Neuilly-sur-Seine, France): Did
you notice if the decrease of SUV after chemotherapy is a better
prognostic or not?
DR OKEREKE: No, that wasn’t included in our study. No, we
did not include patients who underwent neoadjuvant chemora-
diation in this study.