ORIGINAL ARTICLE
Value of integrated PET/CT in detection of hepatic
metastatic deposits
Susan Adil Ali
*, Yasser Ibrahim Abd Elkhalek
Radiodiagnosis Department, Ain Shams University, AL-Abbaseya, Cairo, Egypt Received 18 December 2015; accepted 26 March 2016
Available online 9 April 2016
KEYWORDS CT;
PET; PET/CT; Hepatic metastasis
Abstract Purpose: The goal of this study was to assess the value of combined PET/CT using 18F-FDG in detection and characterization of hepatic metastatic lesions compared to isolated PET and CT in various malignancies.
Patients and methods: The study included 82 patients divided into six groups of primary malignan-cies to whom PET/CT scans were done. Detailed retrograde lesion based and patient based analyses were performed for 441 detected hepatic lesions in 82 patients to detect metastasis on PET, CT and PET/CT. A final diagnosis of metastasis was confirmed by biopsy or by further clinical and radio-logic work-up.
Results: Regarding lesion based analysis, the PET/CT showed 98% sensitivity, 100% specificity, 100% PPV, 84% NPV and 98% accuracy compared with 98%, 98%, 99.7%, 84% and 98%, respec-tively, for PET, and 95%, 81%, 98%, 63% and 94%, respecrespec-tively, for CT. In patient-based anal-ysis, PET/CT and PET showed 99% sensitivity, 100% specificity, 100% PPV, 90% NPV and 99% accuracy compared with 100%, 56%, 95%, 100% and 95%, respectively for CT. The combined PET/CT has significantly improved the low CT sensitivity as well as both CT and PET specificities. Conclusion: PET/CT provides accurate detection of hepatic metastasis and their metabolic nature which significantly affect further management.
Ó 2016 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
The liver is the commonest site of hematogenous metastatic spread. Hepatic metastatic focal lesions are 18–40 times more common than primary hepatic cancers (1). Metastases can
result from a wide variety of neoplasms, the most common being from colorectal, breast, and primary lung cancers (2). Recent advances in different imaging techniques increased the ability to detect and characterize hepatic focal lesions, with improvements in diagnosis and monitoring of liver metastases (3). Unlike conventional imaging, (PET) positron emission tomography combined with (CT) computed tomography (PET–CT) allows an evaluation of the physiological and bio-chemical processes underlying malignant disease. 18F-FDG PET/CT shows high accuracy and sensitivity in the detection of hepatic metastases derived from a wide range of primary
* Corresponding author.
E-mail addresses:Dr.susanadil@hotmail.com(S.A. Ali),yasserib77@ gmail.com(Y.I. Abd Elkhalek).
Peer review under responsibility of The Egyptian Society of Radiology and Nuclear Medicine.
Egyptian Society of Radiology and Nuclear Medicine
The Egyptian Journal of Radiology and Nuclear Medicine
www.elsevier.com/locate/ejrnm
www.sciencedirect.com
http://dx.doi.org/10.1016/j.ejrnm.2016.03.014
0378-603XÓ 2016 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
malignant neoplasms(4). 18F-FDG PET has also been shown to be useful in assessing the chemotherapy treatment response of hepatic metastases(5)especially in colorectal cancer(6). The goal of our study was to assess the value of combined PET/CT using 18F-FDG in detection and characterization of metastatic hepatic focal lesions compared to isolated PET and CT in var-ious malignancies.
2. Patients and methods 2.1. Patients
The study was performed in a retrospective way. The study population included 82 cancer patients (48 male patients, 34 female patients; mean age: 57.5; age range: 36–79) who under-went whole body combined PET/CT scanning. The indications for PET/CT examination were variable; 27 patients were referred for initial disease staging and 55 patients for follow-up at variable disease stages. According to the type of primary malignancies, the study population were divided into six groups. The type of primary malignancy has been histopatho-logically proven for all patients. The study excluded those who had recent intervention (biopsy), radiotherapy or chemother-apy within 1 month from PET/CT scan.
2.2. PET/CT acquisition and processing
Combined PET/CT scan was performed using a hybrid PET/ CT system (Ingenuity, TF PET/CT/Philips, the Netherlands). The integrated CT system is a 64 multi-slice scanner. The acqui-sition of co-registered CT and PET images was performed in one session. Adequate patient preparation rules were strictly followed. Patients were instructed to fast except for glucose-free hydration for 4–6 h before injection of 18F-FDG. The scan was performed 40–60 min after IV injection of 3.7 MBq/kg (maximum dose 370 MBq) equivalent to 0.1 mCi/kg (maxi-mum dose = 10 mCi) of 18F-FDG. The patients were exam-ined in supine position. A whole body examination was performed starting from skull base to mid thighs.
A PET emission scan was performed over several bed posi-tions (5–7), each with an axial field of view of approximately 15 cm per bed position with an in-plane spatial resolution of 4 mm covering the same field of view as with CT. The acquisi-tion time of emission data was 2 min per bed posiacquisi-tion in the time range that was between 13 and 17 min.
A fully diagnostic CT scan was performed using the follow-ing parameters: 350 mA, 120 kV, 0.5 s tube rotation time, slice thickness 5 mm, 8-mm table feed and 3 mm incremental recon-struction. IV contrast administration (80–120 mL) of a low-osmolarity iodinated contrast agent and negative oral contrast agent (water) for bowel was used.
All PET, CT and PET/CT images were reconstructed and viewed on Philips workstation, which provided multi-planar reformatted PET, CT and fused PET/CT images with linked cursors as well as 3D maximum intensity projection (MIP) PET images in video mode.
2.3. Image analysis
A combined team, including one experienced nuclear medicine physician and one experienced radiologist, interpreted the
PET, CT and fused PET/CT images. The PET images were reviewed by the nuclear medicine physician. The CT images were analyzed by the radiologist. Fused PET/CT images were then analyzed separately by each of them, and each was blind to the other’s findings. They were aware of each patient’s his-tory and clinical data. The presence of hepatic metastases was confirmed by biopsy or sequential various imaging modalities including CT, PET/CT, magnetic resonance imaging (MRI); performed during a follow-up of at least 6 months. In some cases reviewing previous scans CT, MRI or PET/CT was also done to correlate recorded lesions.
2.3.1. Lesion based analysis
All focal lesions of abnormal FDG uptake were recorded and assessed quantitatively by measurement of the maximum standardized uptake value (SUV max) for every lesion, and malignant tumors tend to have SUV max values greater than 3.5 and exceeding background activity (by measuring SUV max value at surrounding liver parenchyma or medi-astinal blood pool in cases of diseased liver). Abnormalities detected in the enhanced CT portion of the PET/CT study were recorded, and then each lesion in the fused PET/CT images was also evaluated. The metastatic deposits were either non- enhancing, having marginal enhancement or intensely enhancing unlike cysts with fluid density or heman-giomas that show progressive contrast filling in dynamic scans. Changes in lesion definition and localization provided by PET/CT were recorded. Our standard of reference was histopathologic examination or clinical and imaging follow-up evaluation for at least 6 months together with confirma-tion of diagnosis by other modalities such as MRI used to characterize some of the lesions. A lesion was considered true-positive (TP), if it exhibited progression at 6 months of follow-up imaging, having other modality confirming the diagnosis of the lesions or if the histologic findings were positive. A lesion was considered true-negative (TN), if the lesion was unchanged at follow-up imaging and without clinical deterioration for at least 6 month or if the histologic findings were negative and also if the patient performed other examination such as MRI for evaluation of this lesions and confirmed its benign nature. A false negative (FN) lesion was considered when it was missed by the imag-ing modality and was positive histologically or confirmed to be metastatic by other modality. On the other hand, a false positive (FP) lesion was detected on the imaging study, yet, proved to be negative histologically or by other modality.
2.3.2. Patient based analysis
A CT, PET or PET/CT study that showed at least 1 focal lesion characterized as malignant and that was further con-firmed to be malignant, was considered as true positive, and study of all lesions characterized as benign that showed no evi-dence of active cancer for at least 6 months was considered as true-negative. Study of a patient with positive CT, PET or PET/CT who had no evidence of malignancy on biopsy or other imaging modalities, or a negative clinical follow-up of at least 6 months, was classified as false-positive, and on the other hand a negative CT, PET or PET/CT study in a patient who had further evidence of malignancy during the follow-up was defined as false-negative.
3. Results
82 patients with histopathologically proven primary malig-nancy (Table 1), were evaluated for suspected hepatic metasta-sis using combined PET/CT scans. Metastatic hepatic deposits were found in 77 patients, and 5 patients were free from hep-atic metastases.
3.1. Role of PET/CT in characterization of lesions: lesion-based analysis
There were 441 focal lesions in the 77 patients evaluated (Table 2). Based on PET, CT and PET/CT, 371 lesions were characterized as active metastatic deposits and confirmed histopathologically or on follow-up imaging (Figs. 1 and 2). PET and PET/CT enabled the retrospective detection of 20 lesions missed or not considered pathologic on CT. Malig-nancy was confirmed in 8 lesions by histologic specimens obtained at surgery, by changes on follow-up imaging or con-firmed by MRI study, although they were negative on PET and PET/CT and interpreted as false negative. In 8 focal lesions the CT study was defined as false positive for malignancy, whereas the PET and PET/CT studies were true negative as these focal lesions were non-viable (necrotic). None of these 8 focal lesions developed a recurrence on 6 months of follow-up. One lesion is defined as false positive on PET study due to active pulmonary nodule based on the diaphragmatic pleura of right lung falsely interpreted as a metastatic deposit at the dome of the liver; however, it was confirmed to be pulmonary on both CT and PET/CT (Fig. 3). The remaining 33 lesions were benign lesions (simple cysts, hemangiomas and calcified granulomas) being negative on PET/CT, PET and CT studies and interpreted as true negative and were confirmed by other modalities.
According to the aforesaid data we calculated and com-pared the performance indices of CT, PET and PET/CT for characterization of 441 lesions in 77 patients as regards sensi-tivity, specificity, positive predictive value (PPV), negative pre-dictive value (NPV) and accuracy (Table 3). PET/CT showed sensitivity of 98%, specificity of 100%, PPV of 100%, NPV of 84% and accuracy of 98% compared with 98%, 98%, 99.7%, 84% and 98%, respectively, for PET, compared with 95%, 81%, 98%, 63% and 94%, respectively, for CT data. 3.2. Evaluation of PET/CT diagnostic accuracy: patient-based analysis
82 patients were evaluated for suspected hepatic metastases (Table 4). CT, PET and PET/CT were true negative in 5 as
they had no evidence of hepatic metastases. Hepatic metastases were the final diagnosis in 77 patients. 72 positive PET/CT studies were true-positive with metastases proven by histologic tissue sampling in 41 patients (about 57% of patients) and by other imaging during a follow-up of 6 months in 31 patients (about 43% of patients). Four negative PET/CT were true neg-ative showing necrotic non-viable metastases on histopatho-logic sampling. These were also true negative on PET study, yet false positive on CT. On the other hand, one negative PET/CT study was false-negative with evidence of malignancy on histopathological sampling. This patient had hepatic metas-tases from lung carcinoid tumor which is metabolically inert on PET and PET/CT as well its hepatic deposits; however, it was true positive on CT (Fig. 4). PET and PET/CT showed sensitivity of 99%, specificity of 100%, PPV of 100%, NPV of 90% and accuracy of 99%. CT showed sensitivity of 100%, specificity of 56%, PPV of 95%, NPV of 100% and accuracy of 95%.
4. Discussion
Contrast-enhanced multidetector-row CT is the primary imag-ing modality for the detection, localization, and characteriza-tion of focal liver lesions in many hospitals (7). Several investigators have examined the incremental value of FDG PET as a supplement to CT and found that FDG PET offers information beyond that from CT alone and that this informa-tion often affects patient care(8–10). FDG PET is highly sen-sitive for the detection of liver metastases (11–14), and currently FDG PET/CT is considered the most sensitive non-invasive imaging method for the detection of hepatic metastases, particularly from the gastrointestinal tract (15). A recent meta-analysis demonstrated the sensitivities of CT and FDG PET for detecting hepatic metastases from CRC to be 83.6% and 94.1%, respectively(14). A study of PET– CT for the detection of recurrent or metastatic disease in patients with a history of CRC and raised CEA found PET– CT to be considerably better than multislice CT alone(16). Another study concluded that routine FDG-PET/CT assess-ment of patients with hepatic metastasis has a significant impact on disease staging and selection of candidates suitable for solitary liver metastasis resection and outcome(17).
In a patient-based analysis conducted by Abdel-Nabi et al., they have shown that it can be superior to CT for detecting liver metastasis. They reported sensitivity and specificity rates
Table 1 Number of cases and their histopathologically proven primary malignancy in the 82 patients.
No. of cases Primary malignancy
27 Cancer breast 23 Bronchogenic carcinoma 12 Cancer colon 8 Pancreatic carcinoma 7 Ovarian carcinoma 5 Malignant mesothelioma
Table 2 The CT, PET and PET/CT results, histopathology and/or follow-up for assessment of 441 lesions in 77 patients.
No. of focal lesions PET/CT PET CT Histopathology and/or follow-up 371 TP TP TP POSITIVE 20 TP TP FN POSITIVE 8 FN FN TP POSITIVE 8 TN TN FP NEGATIVE 1 TN FP TN NEGATIVE 33 TN TN TN NEGATIVE
true-positive TP; true-negative TN; false-positive FP; false-negative FN.
Fig. 1 74 years old male with history of lung cancer and hepatic metastatic deposits received CTH and referred for follow-up. (a) CT image shows two metastatic focal lesions at subsegments III and VII. (b) and (c) PET and PET/CT images show that both lesions show increased 18F-FDG uptake with SUV max 9.1 and 7.6 respectively.
Fig. 2 30 years old male with recently diagnosed cancer colon and referred for initial staging. (a) CT images show multiple focal lesions at subsegments IV and VII. (b) and (c) PET and PET/CT images show that these lesions are metabolically active with increased 18F-FDG uptake showing SUV max 5–6.
of 88% and 100%, respectively, with FDG-PET, compared with sensitivity and specificity rates of 38% and 97%, respec-tively, with CT (18). In this study, according to the patient based analysis, we found that PET/CT and PET showed
sensitivity of 99%, specificity of 100%, PPV of 100%, NPV of 90% and accuracy of 99% compared with 100%, 56%, 95%, 100% and 95%, respectively, for CT. So, combined PET/CT improves the low CT specificity and increased its accuracy.
Another lesion-based analysis on the same study conducted by Abdel-Nabi et al., revealed on the basis of PET/CT a sen-sitivity, specificity, and accuracy of 100%, 89%, and 97%, respectively, and a PPV and NPV of 97% and 100% and on the basis of PET a sensitivity, specificity, and accuracy of 96%, 50%, and 85%, respectively, and a PPV and NPV of 85% and 82%, respectively (18). According to Orlacchio et al., the PET study had 94.05% sensitivity, 91.60% specificity and 93.36% accuracy; the CT study had 91.07% sensitivity, 95.42% specificity and 92.29% accuracy. The combined PET/CT had 97.92% sensitivity, 97.71% specificity and 97.86% accuracy(19). In a study by Zidan et al., in 2015 a
mul-Fig. 3 41 years old female with history of endometrial carcinoma underwent TAH BSO, received CTH and RTH, and referred for follow-up. (a) PET image shows a metabolically active lesion falsely interpreted to be at the dome of the liver. (b) CT, (c) axial PET/CT and (d) coronal PET/CT images confirmed the pulmonary location of the nodule (active nodule at the base of right lung based on the diaphragmatic pleura). Multiple other metabolically active pulmonary as well as subcarinal and left hilar LNs is also noted.
Table 3 Comparison of performance indices of CT, PET and PET/CT for characterization of 441 lesions in 77 patients (lesion-based analysis).
No. of lesions TP TN FP FN Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%)
PET/CT 441 391 42 0 8 98 100 100 84 98
PET 441 391 41 1 8 98 98 99.7 84 98
CT 441 379 34 8 20 95 81 98 63 94
Table 4 Comparison of Performance Indices of PET/CT, PET and CT based on patient-based analysis in 82 patients.
Indices PET/CT PET CT
TP 72 72 73 TN 9 9 5 FP 0 0 4 FN 1 1 0 Sensitivity (%) 99 99 100 Specificity (%) 100 100 56 PPV (%) 100 100 95 NPV (%) 90 90 100 Accuracy (%) 99 99 95
timodality assessment of hepatic focal lesions found that, on a lesion based analysis, the sensitivity, specificity, PPV, NPV and accuracy were 94%, 75%, 94%, 75%, and 90% for PET/CT compared to 94%, 95%, 99%, 97% and 94% for MR, respec-tively. Combined PET/CT-MR diffusion raises those parame-ters up to 100%(20). In the present study, according to lesion-based analysis, PET/CT showed sensitivity of 98%, specificity of 100%, PPV of 100%, NPV of 84% and accuracy of 98% compared with 98%, 98%, 99.7%, 84% and 98%, respectively, for PET and sensitivity of 95%, specificity of 81%, PPV of 98%, NPV of 63% and accuracy of 94%, for CT. So, PET/ CT was superior to PET and CT regarding the specificity (100%, 98%, and 81%, respectively) but superior only to CT regarding the sensitivity (98% for PET/CT compared to 95% for CT) and accuracy (98% for PET/CT compared to 94% for CT).
5. Conclusion
PET/CT improved our ability to detect and characterize meta-static liver deposits, for proper staging which significantly affect further management planning.
Conflict of interest
The authors declare that there are no conflict of interests.
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