Ann Nucl Med (2012) 26:689–697 DOI 10.1007/s12149-012-0628-x
ORIGINAL ARTICLE
Somatostatin receptor scintigraphy with 111In-octreotide in pulmonary carcinoid tumours correlated with pathological and 18FDG PET/CT findings Serkan Kuyumcu • Isik Adalet • Yasemin Sanli Cuneyt Turkmen • Zeynep Gozde Ozkan • Dilek Yilmazbayhan
•
Received: 2 May 2012 / Accepted: 20 June 2012 / Published online: 17 July 2012 Ó The Japanese Society of Nuclear Medicine 2012
Abstract Purpose Pulmonary carcinoid (PC) tumors are rare neoplasms of the lung with good prognosis but diagnosis may be demanding since there is no exclusive modality alone to clearly differentiate a PC tumor. The purpose of this study is to establish the diagnostic features of somatostatin receptor scintigraphy (SRS), comparatively (where available) with 18FDG PET/CT (PET/CT) correlated with histopathologic findings. Methods Twenty-one patients who underwent SRS with 111 In-octreotide and were diagnosed as having PC tumors were retrospectively studied. Thirteen patients were performed PET/CT. Primary tumour size, Ki-67 indexes, image analysis data of SRS and PET/CT including maximum standardized uptake values (SUVmax) together with false negative, false positive, true positive and true negative lesions were documented and discussed. Results Eleven (52.4 %) patients were typical (TC) and 10 (47.6 %) were atypical carcinoids (AC) with mean Ki-67 indexes of 2.1 and 24 %, respectively. Patients underwent SRS for solitary pulmonary nodule (SPN) characterization (n = 12) and determination of disease extension (n = 9). Overall sensitivity and specificity of SRS in the detection of primary tumour, lymph nodes (LN) and distant metastasis (DM) were 76 and 97 %, respectively, whereas, positive and negative predictive values were 95 and 86 %. S. Kuyumcu (&) I. Adalet Y. Sanli C. Turkmen Z. G. Ozkan Department of Nuclear Medicine, Istanbul Medical Faculty, Istanbul University, 34390 Fatih, Istanbul, Turkey e-mail:
[email protected] D. Yilmazbayhan Department of Pathology, Istanbul Medical Faculty, Istanbul University, Fatih, Istanbul, Turkey
PET/CT was performed for determining disease spread (n = 3) and metabolic characterization (n = 10) of SPNs. Mean SUVmax in the primary pulmonary lesion in TCs and ACs were 2.9 ± 0.8 and 7.9 ± 5.4, respectively. Nodal involvement (n = 5) and DM (n = 3) were also detected. Sensitivity and specificity of PET/CT in the detection of primary tumour, LNs and DM were 85 and 89.4 %, respectively. Conclusion SRS is useful in the diagnosis and monitoring of PC tumors when incorporated with 18FDG PET/CT as a primary staging tool particularly in the determination of disease spread. Keywords Pulmonary carcinoid Somatostatin receptor scintigraphy FDG PET Ki-67
Introduction PC tumors are rare neuroendocrine neoplasms, which account 1–2 % of all lung malignancies [1]. According to the World Health Organisation criteria [2], lung tumors with neuroendocrine differentiation include four major categories of morphologically identifiable neuroendocrine tumors (NET) from low-grade and intermediate-grade (TC and AC, respectively) to high-grade tumors (large-cell neuroendocrine carcinoma and small-cell lung carcinoma) that exhibit considerably different histological and clinical characteristics [3, 4]. While patients with PC tumors generally have good prognosis after radical surgery, early and specific diagnosis is important since regional LN or DM may be presented or develop over time [5]. PET/CT is increasingly used in the diagnostic work-up of solitary pulmonary nodules (SPNs) that are suspected to be malignant. PC tumors are indolent tumors which usually
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have less FDG uptake than expected and FDG has been thought to be of limited use in the evaluation of these patients [6, 7]. However, carcinoids may also have increased FDG uptake and thus high metabolic activity and malignant potential [8] which make differentiation more challenging. Neuroendocrine markers and hormonal receptors have also been described in carcinoids having diagnostic, prognostic and therapeutic implications [9] such as synthetic somatostatin analogues which have been widely employed in the clinical practice [10]. Despite the progress in diagnostics of NETs in the last decade, a significant proportion of PC tumors are recognized in advanced stage of the disease. Unlike functional imaging procedures such as FDG PET/CT and somatostatin receptor scintigraphy (SRS) conventional imaging techniques provide precise anatomical information but are of limited diagnostic and prognostic value with regard to the functionality of neuroendocrine disease [11]. In this study, retrospective diagnostic SRS data are discussed comparatively (where applicable) with performance of 18FDG PET/ CT for the detection of primary tumor and metastatic sites in patients with proven PC tumors correlated with Ki-67 expression values which have been shown to be of prognostic value in NET of the lung [12].
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slice CT (CT component of BiographTM TruePointTM PET/ CT) with a slice thickness of 4 mm. The CT images and reconstructed SPECT images were evaluated after fusion images were rendered using Siemens SYNGOTM software. 18
FDG PET/CT protocol
All patients were asked to come for PET/CT with at least 4 h of fasting. Images were obtained on a dedicated PET/ CT scanner (BiographTM TruePointTM PET/CT), 60 min after intravenous injection of 370 MBq of FDG. CT acquisition was performed on spiral 4 slice CT with a slice thickness of 4 mm. After transmission scan, 3D PET acquisition was taken for 3 min per bed position for 6–8 bed positions. CT-based attenuation correction of the emission images was employed. PET images were reconstructed by iterative method ordered subset expectation maximization (2 iterations; 8 subsets) with filter size of 5 mm. After completion of PET acquisition, the reconstructed attenuation corrected PET images, CT images and fused images of matching pairs of PET and CT images were available for review in axial, coronal, and sagittal planes and in maximum intensity projections, 3-dimensional cine mode. Histopathological examination data
Materials and methods Out of 236 patients whom were performed SRS in our department between 2004 and 2011, 21 patients with histopathologically proven PCs were retrospectively studied. SRS protocol Patients were well hydrated before and for at least 1 day after injection. Patients were administered 222 MBq (6 mCi) of 111In-pentetreotide, a [111In-DTPA-D-Phe-] conjugate of octreotide and a long-acting somatostatin analogue (OctreoScan). Image acquisition was performed using a large-field-of-view gamma camera fitted with a medium-energy collimator. Symmetrical 20 % energy windows were centered over both photopeaks of 111In (173 and 247 keV) and the data from both windows were added. Whole body scan and planar imaging were performed 4 h after injection. Planar localized images of chest, abdomen and pelvis where necessary were acquired for 20 min using 256 9 256 word matrix. Late planar images and SPECT images of the appropriate regions, as indicated based on the clinical history were acquired 24 h after injection according to the following parameters: 64 frames, 128 9 128 matrix, 360° rotation, 40 s/frame. In 4 patients CT acquisition of the appropriate regions was performed on spiral 4
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The diagnosis of primary tumor was established on the basis of histopathological examination incorporating Ki-67 staining for all patients. Considering patients who underwent SRS and/or FDG PET/CT due to metabolic characterization of SPNs prior to surgery, mediastinal LNs detected in SRS and/or PET/CT were histopathologically examined. Suspected LNs detected in SRS and/or PET/CT of 2 patients were histopathologically confirmed by endobronchial ultrasonographic-guided biopsy. Metastatic soft tissue at the thoracic wall of patient #1 was also histopathologically confirmed. Image analysis SRS and FDG PET/CT studies were reviewed for areas of abnormally increased tracer uptake by an experienced nuclear medicine physician. A positive scan was defined as significant accumulation of tracer based on visual assessment. All detected lesions were documented as LNs and DM in all patients, whereas primary tumors were evaluated for patients with SPNs indicated for metabolic characterization. False positive/negative results, maximum standardized uptake value (SUVmax) of primary lesions, tumour size based on histopathology reports and Ki-67 indexes were reviewed. SUVmax higher than 2.5 was defined as positive in FDG PET/CT. The confirmation of
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imaging was based on histopathological findings in all patients for primary tumors and LN metastasis, whereas confirmations of DM were based on clinical and radiological follow-up. Statistical analysis The differences in Ki-67 index, SUVmax and tumor size between TCs and ACs were analyzed using the Mann– Whitney U test. Spearman’s correlation test was performed in order to analyze relation between the variables. A value of p \ 0.05 was considered statistically significant.
Results Twenty-one patients (6 males, 15 females, age range 17–72) with PC tumors were studied. Twelve patients were presented as having SPNs and underwent SRS for characterization of SPNs, whereas 9 patients were indicated for evaluation of disease spread. 18FDG PET/CT was performed in 13 patients. Ten patients prior to SRS (5.4 ± 2.2 weeks) and 3 patients after surgery following SRS (13.2 ± 9.3 weeks) underwent 18FDG PET/CT. No patients were treated during the interval between the two scans. Mean follow-up time of patients was 44 months at the time of this study. Follow-up times of 5 patients were more than 5 years. Two patients died at 57th and 63rd months after initial diagnosis.
Fig. 1 SPECT images demonstrate 111In-octreotide uptake a in the metastatic soft tissue and b at the left thoracic wall
Results of histopathologic examination data Histopathological examinations of primary lesions demonstrated TCs in 11 patients (52.4 %) and ACs in 10 (47.6 %). Histopathological examinations of mediastinal LNs revealed metastases in 7 patients and reactive proliferation in 2 patients. Mean tumor size and Ki-67 index were 16.5 ± 5.4 mm and 2.72 ± 2.19 %, respectively, in TCs; 20.7 ± 11.2 mm and 22.5 ± 16.1 % in ACs. Ki-67 index was significantly different between TCs and ACs (p \ 0.05), whereas tumor size was not (p [ 0.1). Tumor size was not correlated to Ki-67 values (rs = 0.06, p = 0.4). SRS results All 12 patients (5 AC, 7 TC) with SPNs had radiotracer uptake in the primary tumor. Nine patients were performed SRS within 2 months after surgery in order to determine disease spread. SRS true positively detected radiotracer uptake in the mediastinal LNs in 4 patients but was false negative in 3 patients. Metastases in the thoracic wall
(n = 1; Fig. 1), bone tissue (n = 1) and liver (n = 2) were true positively detected in 4 patients. SRS failed to detect bone metastases in 2 patients. Uptake due to inflammation in the lungs was interpreted false positively in 1 patient. 18
F-FDG PET/CT scan results
In 10 of 13 patients (6 TC, 4 AC) whom were performed FDG PET/CT prior to SRS for metabolic characterization (Fig. 2) of SPNs, mean SUVmax of the primary lesion were 2.9 ± 0.8 and 7.9 ± 5.4 for TCs and ACs, respectively. In 8 patients primary lesions showed significant FDG uptake while in 2 patients (TC) FDG uptake was faint (SUVmax \ 2.5). SUVmax was significantly different between TCs and ACs (p \ 0.05). Mean Ki-67 indexes of patients whom were performed PET/CT were 25.7 ± 16.4 and 2.8 ± 2.6 % for ACs and TCs, respectively. Although there was a correlation between SUVmax and Ki-67 index, it was not statistically significant (r = 0.59, p = 0.07). There was no statistically significant correlation between
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Fig. 2 FDG uptake (SUVmax = 4.2) is demonstrated in the pulmonary lesion of a patient with atypical carcinoid tumour at superior lobe of left lung with FDG PET/CT
SUVmax and tumor size (rs = 0.3, p = 0.3). Mediastinal LNs of 2 TCs showed false positive FDG uptake due to histopathologically proven reactive proliferation. PET/CT true positively detected mediastinal LN metastases (n = 4) as well as DM in bone tissue (n = 2) and liver (n = 1) in 3 patients but was false negative in detecting liver metastasis (#13) in 1 patient. Comparative SRS results with
18
F-FDG PET/CT scan
False positive LNs of 2 TCs (#14, #9) in PET/CT were true negative in SRS. In contrary to PET/CT, SRS was false negative in detecting nodal involvement in 2 ACs (#12, #17). SRS was also false negative in detecting LN metastasis in a patient (#8) who lacked PET/CT. PET/CT was false negative in 1 (#13) of 2 TCs with liver metastasis demonstrated by SRS (#13, #19) but true positive in patient #19 (Fig. 3). Two patients (#16, #17) had bone metastasis and 1 patient (#18) had residual tumor uptake which were only demonstrated by PET/CT. Table 1 summarizes patient data, and histopathological data together with SRS and PET/CT findings.
Discussion Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with g-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. High density of somatostatin receptors found on many cells of endocrine-related tumors including carcinoid tumors has led SRS to become a common procedure for imaging of carcinoid tumors. Regarding gastroenteropancreatic NET, SRS with 111 In-octreotide has proven to be useful, but the number of
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literature evaluating its use in PC tumors, especially comparing it to other modalities, is limited due to rarity of PCs. Yellin et al. [13] has found the sensitivity, specificity, NPV and PPV of SRS in detecting primary tumor, LNs and DM to be 90, 83, 91 and 83 %, respectively. In this study, sensitivity and specificity of SRS in the detection of primary tumor, LNs and DM were 76 and 97 %, respectively, whereas PPV and NPV were 95 and 86 %, respectively. Other than 111In-octreotide, recent development of novel PET tracers, particularly 68Ga-DOTA-peptides has allowed PET/CT imaging of somatostatin receptors which have been reported to present a higher sensitivity for the detection of well-differentiated NETs (WDNT) [14–16]. Jindal et al. [17] reported results of 20 patients (13 TC, 7 AC) whom were performed 68Ga-DOTATOC PET/CT, indicating that it is useful in the evaluation and diagnostic follow-up of PC patients. 68Ga-labeled peptides have been used recently in our department but given the retrospective nature of this study, it was not possible to perform PET/CT imaging of somatostatin receptors. Although FDG PET/CT has proven its utility in differentiating benign and malignant nodules [18], it is not considered to be ideal for PCs which usually have less FDG uptake [5]. Chong et al. [19] found no FDG uptake or less than mediastinum in 4 patients with PC tumors (2 TC, 2 AC) out of 7 pulmonary NETs. Erasmus et al. [6] also found 6 of 7 PC tumors to be hypometabolic. However, carcinoids may also have increased FDG uptake and malignant potential. Daniels et al. [7] reviewed 16 PC patients (11 TC, 5 AC) and reported sensitivity of FDG PET as 75 % and concluded that FDG PET/CT was useful for the evaluation of PCs. Kru¨ger et al. [20] concluded that FDG PET/CT improved accurate localization of metabolic activity in pulmonary lesions on CT in their study where 13 PC patients were evaluated. In this study, sensitivity, specificity and accuracy of PET/CT in detecting primary
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Fig. 3 111In-octreotide uptake in planar SRS images (a) and hypermetabolism (b, c) in the metastatic liver lesion of a patient with typical pulmonary carcinoid tumour
lesion, LNs and DM were 85, 89.4 and 87 %, respectively. Relatively higher sensitivity and specificity in favor of PET/CT might be a consequence of patient selection bias as well as higher than expected ratio of AC to TC among patients whom were performed PET/CT. Additionally, patient data analyzed in this study only included PET/CT
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studies of patients whom were performed SRS, so the number of possible false-negative lesions might have been underestimated. Studies evaluating SRS with 111In-octreotide comparing it to 18FDG PET/CT in carcinoid tumors is also limited. Belhocine et al. [11] evaluated SRS and 18FDG PET/CT and concluded that PET should be reserved to patients with negative results on SRS and SRS remained the modality of choice in carcinoid tumors. Binderup et al. [21] compared performance of SRS with 18FDG PET/CT and 123I-MIBG in 96 patients, 7 of which were PC tumors and found SRS to be more sensitive in functional imaging of NETs. However, as a common ground of recent studies comparing 18 FDG PET/CT to somatostatin receptor imaging with 68 Ga-DOTA-peptides, mean SUVmax values with 18FDG PET/CT for ACs compared to TCs were also higher in this study. Kayani et al. [22] compared 68Ga-DOTATATE to 18 FDG PET/CT in 18 patients, 13 of which were PC tumors (11 TC, 2 AC) and concluded that TC tumors showed lower FDG uptake than of 68Ga-DOTATATE. In a study comparing results of 18FDG PET/CT and 68Ga-DOTATOC PET/CT in 20 PC patients, Jindal et al. [23] found ACs to have significantly higher uptake on 18FDG PET/CT whereas 6 of 7 TCs failed to reveal significant uptake with 18 FDG PET/CT. 18 FDG PET has been reported to be of value in patients with negative SRS or high proliferation index (Ki-67 [ 15 %) [11]. SRS was false negative in 4 patients, 3 of which were ACs (#12, #16, #17) where PET/CT true positively detected FDG uptake. Histopathologic grade of the tumor as well as various factors such as size, tumor type and expression of the receptor subtypes and their density on the tumor cell surface [24] may lead to false negative SRS. Furthermore, as a pitfall of SRS [5], radiotracer uptake at non-tumor sites can yield false-positive results since somatostatin receptors are overexpressed in granulomatous and inflammatory processes [25] such as post-surgical inflammation (patient #7). SPECT/CT may be useful in this manner in order to overcome false-positive interpretation of radiotracer uptake. In 3 patients with suspicious faint radiotracer uptake in the abdominal region, SPECT/CT demonstrated physiological colon uptake which diminished in late planar images. In patient #1, metastatic soft tissue was accurately localized (Fig. 1). Number of patients with SPECT/CT in this study is not adequate to draw conclusions on probable incremental value of SPECT/CT over SPECT. However, confident interpretation was of benefit in these patients, but a further study is required in larger samples especially on dedicated SPECT/CT cameras. DM has been reported in percentages that range from 4 to 27 % in TC and 23 to 87 % in AC [26, 27], generally in favor of TC compared to AC [28, 29]. Percentages of DM for TCs (n = 3) and ACs (n = 3) were 27 and 30 %,
123
123
F
F
M
F
M
F
F
M
F
F
M
F
F F
F
M
F
F
M
F
F
1
2
3
4
5
6
7
8
9
10
11
12
13 14
15
16
17
18
19
20
21
66
57
59
38
18
61
64
72 49
29
30
46
41
24
22
52
17
40
41
43
54
Age
31
26
58
20
19
63
57
43 24
30
46
6
56
23
54
96
44
61
49
84
44
Follow-up (months)
TC
AC
TC
AC
AC
AC
AC
TC TC
AC
TC
AC
TC
TC
AC
TC
AC
TC
AC
TC
TC
Type
8
5
3
40
50
30
10
2 1
30
2
15
1
1
3
2
20
4
20
1
5
Ki-67 (%)
13
12
10
15
10
22
8
20 25
25
20
30
8
17
45
20
15
16
25
11
22
Size (mm)
Histopathologic findings
HP ? Fc HPb HP HP ? Fc HP ? Fc
?b ?b ?b ?a
-
-
HP
F
HP
F
HP
?b
-
HP
-
N/A
N/A
?
FN
N/A
?
?
N/A ?
?
?
?
?
-
HP
HPb
-
?
HP
?b
FP
N/A
F
HP
?a
?
N/A
N/A
?
N/A
Pulmonary lesion
-
HP
F
F
HP
HP
Confirmation of imaging
-
-
-
-
-
Lymph node
SRS findings
-
-
-
-
FN
?
?
? -
FN
-
-
-
FN
-
?
-
-
-
-
-
Lymph node
-
-
?
-
FN
FN
-
? -
-
-
-
-
-
-
-
-
-
?
-
?
Distant metastasis
FN
N/A
?
?
N/A
?
?
? ?
?
?
?
FN
Pulmonary lesion
1.9
N/A
3.4
N/A
N/A
15.8
7.4
3.1 4.3
4.37
2.6
4.2
2.2
SUVmax of pulmonary lesion
PET/CT findings
-
-
-
-
?
?
?
? FP
?
-
-
FP
Lymph node
-
-
?
-
?
?
-
FN -
-
-
-
-
Distant metastasis
c
b
a
Histopathologic confirmation of lymph nodes and follow-up of distant metastasis
Post-surgical histopathologic examination
Endobronchial ultrasonography-guided biopsy
N/A not available/evaluated for patients indicated other than metabolic characterization, TC typical carcinoid, AC atypical carcinoid, FN false negative, FP false positive, HP histopathology, F follow-up
Gender
#
Patients
Table 1 Summary of patient data, tumour histopathology, SRS and PET/CT findings
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Table 2 Performance of SRS in detecting primary lesion, metastatic lymph nodes and distant metastasis according to histopathological subtypes Sensitivity
Specificity
PPV (%)
NPV (%)
Typical
91.6
100
100
95.4
Atypical
61.5
94.1
88.9
76.1
Table 3 Performance of SRS in detecting primary lesion, metastatic lymph nodes and distant metastasis Sensitivity
Specificity 88.8
PPV (%)
Primary tumor
91.6
Lymph node metastasis
57.1
100
100
Distant metastasis
66.6
100
100
Overall
76
97.3
91.6
95
NPV (%) 88.8 82.3 93.7 86
respectively, which correlate with the literature. SRS was true positive in all TCs with DM. In 2 patients with liver metastasis whom were performed both modalities, PET/CT was false negative in patient #13 who had a 9-mm metastatic lesion in MRI. This may be due to the size of the lesion as well as lower proliferation rate which makes it more difficult to differentiate pathological uptake especially in liver where physiologic uptake is high. Although TCs are expected to have less FDG avidity, FDG uptake may be of prognostic value in metastatic TCs, but supporting evidence needs to be studied. Unlike TCs, SRS was false negative in 2 out of 3 ACs with DM whereas PET/CT was true positive. ACs tumors are more likely to be FDGavid than TCs. Thus, a negative SRS scan should not be used to exclude metastasis in PCs, especially in ACs. FDG PET/CT may be valuable in this group of patients. Furthermore, a positive SRS scan may be of value in a patient with advanced AC since receptor positivity may be decisive of treatment planning. Nodal involvement has been reported up to 60 % in several studies [30–33]. In this study, overall nodal involvement was 18 % in TC and 40 % in AC patients. SRS was false negative in detecting nodal involvement in 2 patients which were true positively detected by PET/CT. PET/CT detected LN hypermetabolism in 7 patients, 2 of which were false positive due to reactive proliferation. Of 5 patients with true positive nodal involvement with PET/CT 4 patients were ACs whereas 2 patients with false positive nodal involvement were TCs. As regional disease with spread to local LNs occurs most frequently in ACs [5], in cases of FDG-positive LNs in TCs nuclear medicine specialists should exclude other reasons to avoid false-positive interpretation.
Mean follow-up time was 44 months. Since only 5 patients (3 TC, 2 AC) were followed more than 5 years, it is not possible to imply survival rates for TCs and ACs in a relatively small number of samples. On the other hand, 2 ACs (#15 and #16) who had nodal involvement and high FDG uptake (SUVmax 7.4 and 15.8) in the primary pulmonary lesion died at the 57th and 63rd months of followup. These data correlate with the literature reporting 5-year survival rates as low as 25 % for ACs in the lung with nodal involvement [34] and high FDG uptake to be a predictor of bad prognosis in carcinoid patients [35]. PCs are usually presented as SPNs and due to the positivity of other more aggressive thoracic malignancies, it is not uncommon that patients are performed FDG PET/CT prior to SRS. Therefore, SRS may not be the first-line diagnostic imaging modality. This study only includes retrospective PET/CT studies of patients who underwent SRS, thus does not measure the performance of PET/CT in determination of PCs among SPNs. Therefore, this may be why FDG PET/CT as per this study has a higher sensitivity than SRS. However, sensitivity and specificity of SRS were higher in favor of TCs (Table 2) and overall sensitivity and specificity of SRS were higher in the detection of primary tumour than lymph nodal and DM (Table 3). Therefore, the value of FDG PET/CT as a primary staging tool, complementary to SRS particularly in determining LN and DM in ACs, should not be avoided especially in centers where 68 Ga-DOTA-peptides are not available. Recent studies have suggested a prognostic role for FDG PET/CT in WDNT [36] as well, which renewed interest for FDG PET/CT for not only prognosis but also staging in WDNT including PCs. Garin et al. [35] evaluated 38 patients with metastatic NET and found 18FDG PET to exhibit excellent predictive values for early tumour progression which was superior to Ki-67 index alone and suggested that 18FDG PET and SRS results correlate with progression-free and overall survival even for histologically low-grade tumors. Ki-67 index is a powerful discriminator of tumors grade and a prognostic marker in NETs [37] and together with FDG PET they have been reported to be independent predictors of overall survival in NETs [38]. Although there was a correlation between FDG uptake and Ki-67 index, it was not statistically significant (p = 0.07). Therefore, a specific comparison of SUVmax with Ki-67 index in a larger group of patients would have been useful, but lack of FDG PET/CT in all patients has been a limitation of this study.
Conclusions Even though known as indolent tumors, a significant portion of PCs is recognized in advance stage of the disease and given the limited therapeutic options diagnosis is
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challenging. SRS plays a central role in the detection of primary lesions in PCs as well as follow-up monitoring. However, 18FDG PET/CT is also useful in the diagnosis and follow-up of PC tumors complementary to SRS, particularly as a staging tool in the detection of disease spread of ACs. Conflict of interest
The authors declare no conflict of interest.
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