To explore TNM stage and quantitative parameters (SUVmean, SUVmax, MTV, TLG) in small cell lung cancer patients who underwent 18F-FDG PET/CT before initial treatment. Subjects and methods: Retrospective analysis in 32 patients diagnosed with small cell lung cancer based on pathological results at the Oncology and Nuclear Medicine Department, Bachmai Hospital and 61 non-small cell lung cancer patients at 103 Military Hospital, from November 2009 to June 2019. They were underwent 18F-FDG PET/CT-scans before the treatment. The variables include: Location, tumor size, SUVmean, SUVmax, MTV and TLG of the tumor. Results: 32 small cell lung cancer patients (29 males, 3 females) and 61 non-small cell lung cancer patients (45 males, 16 females) with the mean age of 61.3 ± 9.5 and 64.3 ± 9.3, respectively. There was a significant difference of TNM stage between 2 groups. The ratio of expanded stage in non-small cell lung cancer was higher than that in small cell lung cancer (93.4% vs. 71.9%, p < 0.01). The SUVmean and SUVmax of primary tumor were higher in nonsmall cell lung cancer compared to small cell lung cancer.
Trang 1
STUDY ON PET/CT FINDINGS IN PATIENTS WITH
SMALL CELL LUNG CANCER
Bui Anh Thang 1 ; Do Quyet 2 ; Pham Ngoc Hoa 2
SUMMARY
Objectives: To explore TNM stage and quantitative parameters (SUV mean , SUV max , MTV,
TLG) in small cell lung cancer patients who underwent 18 F-FDG PET/CT before initial treatment
Subjects and methods: Retrospective analysis in 32 patients diagnosed with small cell lung
cancer based on pathological results at the Oncology and Nuclear Medicine Department,
Bachmai Hospital and 61 non-small cell lung cancer patients at 103 Military Hospital, from
November 2009 to June 2019 They were underwent 18 F-FDG PET/CT-scans before the
treatment The variables include: Location, tumor size, SUV mean , SUV max , MTV and TLG of the
tumor Results: 32 small cell lung cancer patients (29 males, 3 females) and 61 non-small cell
lung cancer patients (45 males, 16 females) with the mean age of 61.3 ± 9.5 and 64.3 ± 9.3,
respectively There was a significant difference of TNM stage between 2 groups The ratio of
expanded stage in non-small cell lung cancer was higher than that in small cell lung cancer
(93.4% vs 71.9%, p < 0.01) The SUV mean and SUV max of primary tumor were higher in
non-small cell lung cancer compared to non-small cell lung cancer The MTV and TLG of mediastinal
lymph nodes in small cell lung cancer were higher than those in non-small cell lung cancer
Conclusion: PET/CT is a very good image technique in diagnosis and classification of staging of
small cell lung cancer It distributes to distinguish between non-small cell lung cancer and small
cell lung cancer based on the difference of SUV mean , SUV max , MTV and TLG of the tumors
* Keywords: Small cell lung cancer; PET/CT
INTRODUCTION
Lung cancer is one of the most common
tumor types, representing 13% of newly
diagnosed cancers worldwide Both the
absolute and relative frequencies of lung
cancer have risen dramatically Unfortunately,
it remains by far the leading cause of
cancer-related deaths, accounting for 18%
of the total number of deaths [6] Small
cell lung cancer (SCLC) accounting for
10% of clinical lung cancer cases, is an
aggressive malignancy strongly associated
with smoking It displays a distinct natural
history characterized by a high growth fraction, rapid doubling time and early establishment of widespread metastatic lesions [3]
In patients who present with SCLC, it
is important to determine whether the cancer is limited or at an extensive stage
Limited-stage cancer, which is potentially curable, is treated with chemotherapy and radiation, with surgical resection reserved for selected patients with stage I disease
Extensive-stage cancer is incurable; systemic chemotherapy is used to improve quality
of life and prolong survival [8]
1 Pham Ngoc Thach Medical University
2 Vietnam Military Medical University
Corresponding author: Bui Anh Thang (thangcdha@gmail.com)
Date received: 05/07/2019
Date accepted: 26/08/2019
Trang 2
18
F-fluorodeoxyglucose positron emission
tomography-computed tomography
(18F-FDG PET/CT), which provides
morphological and metabolic data of
malignancy, has become an important
non-invasive tool for the staging as well
as for the assessment of the primary
tumor and distant metastasis in lung
cancer FDG uptake in the primary tumor
measured as the maximum standardized
uptake value (SUVmax) by PET, which well
known measure indicating the disease
activity or the aggressiveness of tumor,
can be easily obtained and is the most
widely used parameter for the analysis of
18
F-FDG PET images in clinical practice
As we all known, metastasis occurs
primary by dissemination not only through
the lymphatic and blood vessels but local
extension in SCLC
In this study, we aim: To explore TNM
stage and quantitative parameters (SUV mean ,
SUV max , MTV, TLG) in SCLC patients who
underwent 18 F-FDG PET/CT before initial
treatment
SUBJECTS AND METHODS
1 Clinical data
We retrospectively analyzed the 18
F-FDG PET/CT findings of 32 newly diagnosed
SCLC patients from November 2009 to
June 2019, and 61 non-SCLC (NSCLC)
patients as the control group All patients
were defined by histological or
cytological evidences The patients were
referred to Nuclear Medicine and
Oncology Center, Bachmai Hospital and
103 Military Hospital for initial staging with
PET/CT-scan before treatment Histological diagnosis of the tumors was based on the criteria of the World Health Organization (2015) [12] and TNM stage was determined according to the 8th lung cancer TNM classification of International Association for the Study of Lung Cancer
2 FDG PET/CT imaging
18
F-FDG PET/CT-scans were performed with a wholebody PET/CT-scanner All patients had been fasting for at least 6 hours before PET imaging, and serum glucose levels were measured to ensure that the results were 180 mg/dL All patients had a glucose level below 180 mg/dL and were injected intravenously with 0.15 - 0.20 mCi/kg (7 - 12mCi) FDG 45 -
60 minutes after the injection, data were acquired from the vertex to the upper thigh Immediately after CT, a PET-scan (PET/CT Biograph True Point, Siemens, Germany) was performed for about
25 minutes, with seven to eight bed positions and 3 minutes/position PET images were reconstructed iteratively with CT data for attenuation correction, using an inline integrated Siemens Esoft Workstation system CT integrated positron emission tomography fusion images in transaxial, sagittal and coronal planes were evaluated visually, and SUVmax of lesions was obtained from transaxial images
3 Imaging analysis
The PET/CT images were reviewed by using the automatic PET/CT fusion software
on the workstation A volumetric
Trang 3
of-interest (ROI) around the outline of
primary tumor in the SCLC was placed on
the axial PET images using the
semi-automatic software A threshold of 40% of
the maximum signal intensity was selected
to delineate ROI Then SUVmax, SUVmean,
MTV and TLG were automatically calculated
by the PET/CT fusion software and these values were recorded from the workstation Both radiologists who conducted the measurements together were blinded to the clinical details
Figure 1: Measurement of SUV and MTV (Source: Nucl Med Mol Imaging, 2012 [14])
4 Statistical analysis
Statistical analysis was done using SPSS 22.0 (Chicago, Illinois, USA) The mean of
the measurement data was expressed as mean ± standard deviation (mean ± S.D) The differences of SUVmean, SUVmax, MTV and TLG of the tumor in independent groups were compared by using independent t-test P values less than 0.05 were considered signifcantly
RESULTS
Table 1: Chracteristics and TNM staging of SCLC and NSCLC patients
Sex (n, %)
Male
Female
29 (90.6%)
3 (9.4%)
45 (73.8%)
16 (26.2%)
0.055
T stage (n, %)
T1 - T2
T3 - T4
17 (53.1%)
15 (46.9%)
15 (24.6%)
46 (75.4%)
0.012
Trang 4
N stage (n, %)
N0 - N1
N2
N3
9 (28.1%)
11 (34.4%)
12 (37.5%)
6 (9.8%)
26 (42.6%)
29 (47.5%)
0.001
M stage (n, %)
M0
M1a
M1b
M1c
24 (39.3%)
6 (9.8%)
21 (34.4%)
10 (16.4%)
11 (34.4%)
5 (15.6%)
8 (25.0%)
8 (25.0%)
0.545
Overall stage (n, %)
I - II
III
IV
3 (9,4%)
8 (25%)
21 (65.6%)
2 (3.3%)
22 (36.1%)
37 (60.6%)
0.022
32 SCLC patients (29 males, 3 females) and 61 NSCLC patients (45 males, 16 females) with the mean age of 64.3 ± 9.3 and 61.3 ± 9.5, respectively There was not difference of age between two groups There were significant differences of TNM stage between two groups The ratio of extensive stage in SCLC was lower than that in NSCLC (71.9% vs 93.4%, p < 0.01)
Table 2: Metastasis in SCLC compared to NSCLC on PET/CT
Trang 5
All cases of NSCLC has metastasis at least one location (100%) compared to patients with SCLC (84.1%) (p < 0.01) The ratio of mediastinal lymph nodes metastasis was lower and the ratio of lung metastasis was higher in SCLC compared to those in NSCLC
Table 3: SUVmean, SUVmax, MTV and TLG in SCLC and NSCLC
Primary tumors
Mediastinal lymph nodes
The SUVmean and SUVmax of the primary tumors were lower in SCLC than those in NSCLC The tumor size, MTV and TLG of mediastinal lymph nodes were higher in SCLC compared to those in NSCLC
Figure 2: Patient with primary tumor Figure 3: Lung metastasis
Trang 6
Figure 4: Mediastinal metastasis Figure 5: Brain metastasis
Figure 2 - 5 were the PET-CT images of patients with SCLC at stage IV according to
TNM classification
DISCUSSION
Although CT or magnetic resonance
imaging provides precise anatomical and
morphological information, the role of
FDG-PET/CT has increased in diagnosis
and classification of lung cancer staging
[1] Recently, FDG uptake has been
reported to be a prognostic factor in
patients with lung cancer [1, 4 Patz et al
[10] demonstrated that patients with
positive FDG-PET/CT results in treating
lung cancer had a significantly worse
prognosis than patients with negative
results Therefore, we examined whether
SUVmax correlates with tumor size, lymph
node and distant metastases in patients
with SCLC
FDG PET/CT is an important adjunct
examination in evaluating SCLC, combining
functional informations (FDG PET) with
anatomical information (CT) FDG PET/CT
is invaluable in clinical staging and restaging, guiding therapy, and suggesting prognosis SCLC is readily identified at FDG PET because of its high metabolic activity Some studies had reported improved staging accuracy with FDG PET compared with CT alone [2, 11] and FDG PET/CT was more accurate than FDG PET alone Use of FDG PET in combination with conventional imaging has led to upstaging from local stage-SCLC to extensive stage-SCLC in 19% of patients and to downstaging from extensive stage-SCLC
to local stage-SCLC in 8% of patients Although FDG PET is inferior to CT or MRI for the detection of brain metastases,
it is more sensitive and specific than conventional imaging for detecting metastatic disease
Trang 7
18
F-FDG PET/CT has been increasingly
used for staging, treatment response
assessment and therapy planning in
SCLC since it was introduced into clinical
practice in 1998 Apart from qualitative
assessment in the detection of
metastases, PET/CT provides the
opportunity of a semi-quantitative
measure of tumor glycolysis using SUV
SUVmax is the highest SUV measurement
in the ROI and is the most commonly
used measurement in clinical practice
because of its being least affected by
partial volume effects [5] SUVmax is also
defined as a unique noninvasive method
for studying biochemical and metastatic
changes in cancer tissues The relationship
between SUVmax of primary tumor and
local extension, lymph node and distant
organ metastasis was investigated
Our results showed that the the SUVmean
and SUVmax of the primary tumors were
lower in SCLC than those in NSCLC The
tumor size, MTV and TLG of mediastinal
lymph nodes were higher in SCLC
compared to those in NSCLC
SUVmax has been correlated with tumor
proliferation rate, tumor grade, and
expression of glucose transporters, which
are biomarkers in various types of malignant
tumors Metastasis is the major cause of
death due to several malignancies,
including SCLC and it occurs primary by
dissemination through the lymphatic and
blood vessels Nambu et al (2009) had
reported that the likelihood of lymph node
metastasis increased with increase of
SUVmax of the primary tumor in patients
with NSCLC [9] Our results were consistent
with their observations In their study, they also added when the SUVmax of the primary tumor was greater than 12, the probability of lymph node metastasis was high, reaching 70%, irrespective of the degree of FDG accumulation into the lymph node stations This finding would allow us to more sensitively predict the presence of lymph node metastases, including microscopic ones that cannot be detected by a direct evaluation of the lymph node stations
In patients with NSCLC, Zhu et al [15] had shown that the average of SUVmax
was significantly lower in patients without any metastasis than that with lymph node and/or distant organ metastasis These results further suggested that SUVmax may
in partly reflect the potential of metastasis
in primary tumor in NSCLC However, there was no upper threshold of SUVmax of NSCLC, above which lymph node and/or distant organ metastasis were always present Thus, even when a primary tumor
in NSCLC shows high SUVmax exceeding
10 or 20, the presence of lymph node and/or distant organ metastasis is still inconclusive based on the evaluation of the SUVmax of the primary tumor
The utility of PET in the initial staging
of patients with SCLC has been evaluated
in 12 studies comparing pre-treatment
18
F-FDG-PET to conventional staging procedures according to a meta-analysis [7] Study designs varied with regard to the extent of conventional staging, the use of PET alone or PET/CT, and the method used to define PET positivity In addition, some studies required biopsy of
Trang 8
all FDG-avid lesions that would alter stage,
whereas others used clinical follow-up to
confirm PET findings Unfortunately,
several studies did not validate PET findings
and stage alterations by either method
SCLC is a highly metabolic malignancy,
leading to a sensitivity of 100% for PET
detection of primary tumors Overall,
cumulative staging concordance was 84%
between PET and conventional imaging
with better concordance noted in the
prospective (89%, range 83 - 100%) than
the retrospective (80%, range 67 - 100%)
studies [7] Of the 204 patients with local
stage-SCLC by conventional imaging,
19% were up-staged to extensive by PET,
with similar findings in the prospective
(17%, range 0 - 33%) and retrospective
(20%, range 0 - 54%) studies Of the 199
patients with extensive stage-SCLC by
conventional imaging, 11% were
down-staged to local stage by PET, with a much
lower percentage of down-staged patients
noted in the prospective (5%, range 0 -
11%) than retrospective (18%, range 0 -
40%) studies For most metastatic sites,
PET was superior to standard imaging in
both sensitivity and specificity However,
PET was inferior to MRI or CT for the
detection of brain metastases [7]
CONCLUSION
PET/CT is a very good image technique
in diagnosis and staging of SCLC It
distributes to distinguish between NSCLC
and SCLC based on the difference of
SUVmean, SUVmax, MTV and TLG of the
tumors
REFERENCES
1 Al-Sarraf N, Gately K, Lucey J et al
Clinical implication and prognostic significance
of standardised uptake value of primary non-small cell lung cancer on positronemission tomography: Analysis of 176 cases Eur J Cardiothorac Surg 2008, 34 (4), pp.892-897
2 Azad A, Chionh F, Scott A.M et al High
impact of 18F-FDG PET on management and prognostic stratification of newly diagnosed small cell lung cancer Mol Imaging Biol
2010, 12 (4), pp.443-51
3 Gustafsson B.I, Kidd M, Chan A et al
Bronchopulmonary neuroendocrine tumors Cancer 2008, 113 (1), pp.5-21
4 Hanin F.X, Lonneux M, Cornet J et al
Prognostic value of FDG uptake in early stage non-small cell lung cancer Eur J Cardiothorac Surg 2008, 33 (5), pp.819-823
5 Ikushima H, Dong L, Erasmus J et al
Predictive value of 18F-FDG uptake by positron emission tomography for non-small cell lung cancer patients treated with radical radiotherapy J Radiat Res 2010, 51 (4), pp.465-471
6 Jemal A, Bray F, Center M.M et al
Global cancer statistics CA Cancer J Clin
2011, 61 (2), pp.69-90
7 Kalemkerian G.P Staging and imaging
of small cell lung cancer Cancer Imaging
2011, 11, pp.253-258
8 Kalemkerian G.P, Schneider B.J Advances
in small cell lung cancer Hematol Oncol Clin North Am 2017, 31 (1), pp.143-156
9 Nambu A, Kato S, Sato Y et al
Relationship between maximum standardized uptake value (SUV max ) of lung cancer and lymph node metastasis on FDG-PET Ann Nucl Med 2009, 23 (3), pp.269-275
Trang 9
10 Patz E.F Jr, Connolly J, Herndon J
Prognostic value of thoracic FDG PET
imaging after treatment for non-small cell lung
cancer AJR Am J Roentgenol 2000, 174 (3),
pp.769-774
11 Podoloff D.A, Ball D.W, Ben-Josef E et
al NCCN task force: Clinical utility of PET in a
variety of tumor types J Natl Compr Canc
Netw 2009, 7 Suppl 2, pp.S1-26
12 Travis W.D, Brambilla E, Nicholson A.G
et al The 2015 World Health Organization
classification of lung tumors: Impact of genetic,
clinical and radiologic advances since the
2004 classification J Thorac Oncol 2015, 10
(9), pp.1243-1260
13 Yoo S.W, Kim J, Chong A et al
Metabolic tumor volume measured by 18 F-FDG PET/CT can further stratify the prognosis
of patients with stage IV non-small cell lung cancer Nucl Med Mol Imaging 2012, 46 (4), pp.286-2893
14 Zhao M, Chang B, Wei Z et al The role
of 18F-FDG uptake features in the differential diagnosis of solitary pulmonary lesions with PET/CT World J Surg Oncol 2015, 13, p.271
15 Zhu S.H, Zhang Y, Yu Y.H et al FDG
PET/CT in non-small cell lung cancer: Relationship between primary tumor FDG uptake and extensional or metastatic potential Asian Pac J Cancer Prev 2013, 14 (5), pp.2925-2929.