• No results found

Added value of combined 18F-FDG PET/CT for detection of osseous metastases in cancer patients

N/A
N/A
Protected

Academic year: 2021

Share "Added value of combined 18F-FDG PET/CT for detection of osseous metastases in cancer patients"

Copied!
6
0
0

Loading.... (view fulltext now)

Full text

(1)

ORIGINAL ARTICLE

Added value of combined 18F-FDG PET/CT for

detection of osseous metastases in cancer patients

Susan Adil Ali

*

, Yasser Ibrahim Abd Elkhalek

Radiodiagnosis Department, Ain Shams University, AL-Abbaseya, Cairo, Egypt Received 23 February 2016; accepted 11 March 2016

Available online 3 April 2016

KEYWORDS CT;

18F-PET/CT; Osseous metastases

Abstract Purpose: The goal of the study was to illustrate the added value of combined 18F-FDG PET/CT over isolated CT for detection of osseous metastases in cancer patients.

Patients and methods: The study included 53 patients divided into five groups of primary malignan-cies. 18F-PET/CT scans were performed. In this study, a lesion based analysis was performed in detailed retrograde matter for a total of 386 detected osseous lesions on CT and fused images of 18F-PET/CT. Statistical analysis including specificity, Sensitivity, negative predictive value (NPV) and positive predictive value (PPV) of each of these modalities was calculated. A final diagnosis of metastasis was confirmed by biopsy or by further clinical and radiologic workup. Results: According to lesion based analysis, the 18F-PET/CT showed 100% sensitivity, 80.8% specificity, 98.6% PPV, 100% NPV and 98.7% accuracy compared with 93.9%, 34.6%, 95.2%, 29% and 89.9%, respectively, for CT. Significant improvement of the sensitivity and specificity was found in combined 18F-PET/CT than in CT alone.

Conclusion: Combined 18-F FDG PET/CT significantly improves the sensitivity and specificity of isolated CT for the detection of osseous metastases.

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

Metastases are the commonest malignant tumors involving the bony skeleton. Imaging is very important in the diagnosis, detection, planning of treatment and prognostication as well as for follow-up of metastatic boney lesions. In patients with proven non-skeletal tumors, imaging is useful for screening

the skeleton to assess metastatic disease and, if it is present, to determine its extent (1–3). Multislice spiral CT enables imaging of all of the skeleton without any superposition effects and so much more suitable for the accurate detection of metas-tases especially in anatomically complex zones as the spine. CT is highly sensitive for the osteolytic as well as osteoplastic bone lesions affecting cortical bone, but less so for tumors confined to the marrow space, which must be very much extensive to be detectable. And so, CT has limited use as an imaging modality screening for different osseous metastases, in spite of its high specificity (4). ‘‘Positron emission tomography” (PET) is a scan technique of molecular imaging basis widely used in diagnosis of tumoral activity, using ‘‘18F labeled

fluoro-* 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.2016.03.006

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/).

(2)

deoxyglucose (18F-FDG)”. The PET scan gives us functional information in quantitative and qualitative manner about the tumor cells according to their high rate of metabolism of glucose(5). PET scanning can identify osseous metastases at an early stage of growth before host reactions to tumor cells occur. Early malignant bone marrow infiltration can be depicted by 18F-FDG PET because of the very early increased metabolism of glucose in the neoplastic cells(6). The combined PET/CT is unique as it can scan the whole body in one session, and it can provide us with the functional and anatomic data in coregistered images. It combines the value of both CT and PET in best anatomical localization in the CT and activity of lesions by the PET scan and so more accuracy in detection and staging of different malignancies(5). The goal of this study was to assess the value of combined PET/CT using 18F-FDG in detection of osseous metastatic lesions compared to isolated CT in various malignancies.

2. Patients and methods 2.1. Patients

The study is retrospective and population included 53 cancer patients (38 male patients, 15 female patients; the mean age: 53.5; age range: 33–74). They underwent combined PET/CT scanning on whole body. Variable indications for PET/CT examination and they were; 22 patients were referred to the study for initial staging of the disease and 31 patients at different disease stages follow up. According to the malignancy type, the patients were divided into five groups and this was accord-ing to the primary malignancies type. The primary malignancy type has been pathologically proven for all patients. Exclusion criteria were any recent intervention as biopsy or local beam radiotherapy or therapy by ‘‘granulocyte colony stimulating factor” within about 1 month from the PET/CT scan. 2.2. PET/CT acquisition and processing

Combined PET/CT scan using a hybrid PET/CT system (Inge-nuity, TF PET/CT/Philips, the Netherlands) was performed. A 64 multi-slice scanner was the integrated CT system. Both studies and co-registered CT and PET images were performed in a single session. The rules of patient preparation were fol-lowed strictly. Complete fasting except for glucose-free hydra-tion for about 4–6 h before the injechydra-tion of 18F-FDG was instructed to the patients. The scan was performed after IV injection by about 40–60 min using 3.7 MBq/kg, as a dose ‘‘(maximum dose 370 MBq) equivalent to 0.1 mCi/kg; (maximum dose = 10 mCi) of 18F-FDG”. The study was done with patient in supine position. The study was performed on the whole body from the skull base down to the mid thighs. A PET scan with different bed positions (5–7) was per-formed and each with approximately 15 cm axial field of view for each bed position with 4 mm in-plane spatial resolution and was covering the same field of view of the CT. The time of acquisition emission data was about 2 min for each bed position and in time range between 13 and 17 min.

The parameters of the diagnostic CT scan were as follows: 350 mA, 120 kV, 0.5 s was the tube rotation time, the slice thickness was 5 mm and 8-mm table feed. incremental recon-struction about 3 mm. negative oral contrast (e.g. water)

for bowel were used and IV contrast administration of 80–120 mL of iodinated contrast agent with low-osmolarity.

A Philips workstation was used to view All CT, PET and PET/CT images and they were reconstructed in multiplanar reformation and viewed in different planes for all as well as ‘‘3D maximum intensity projection images (MIP)” PET images in a video mode. The study protocol was approved by the local ethics committee.

2.3. Image analysis

A team including a nuclear medicine physician and a radiolo-gist reviewed and interpreted the PET, CT and the fused PET/ CT images and each was blind to the other’s findings. Both were aware of the full patient’s history and relevant clinical data. The bone metastases after that were confirmed by biopsy or by other imaging modalities as PET, CT, PET/CT and magnetic resonance imaging (MRI); all were performed during at least 6 months of follow-up. Reviewing older scans in some cases was done as well to correlate the recorded lesions. 2.3.1. Lesion based analysis

All focal osseous lesions with abnormally high FDG uptake were examined, recorded and accurately assessed first quanti-tatively by the measurement of the ‘‘maximum standardized uptake value (SUV max)” for every boney lesion. The malig-nant tumors have high SUV values that are greater than 3.0–3.5. Different pathologies that were detected in the CT por-tion of study were evaluated and recorded, then each of the lesions in the fused images of PET/CT was evaluated. Histopathologic examination, clinical evaluation and imaging data of follow-up evaluation for at least 6 months were the standard of reference. A suspected osseous lesion was consid-ered as a true-positive if the lesions were positive histologically or if there is remarkable progression at the 6 months of follow-up. The osseous lesion was considered true-negative when there is negative histological findings or if the lesion totally disap-peared or unchanged at the follow-up imaging. Also no clinical deterioration of the patient for at least 6 months has to be fulfilled. A false negative osseous lesion was considered when it was missed by the imaging modality and was positive histo-logically or progressed on follow-up. On the other hand, a false positive lesion was detected on the imaging study, yet, proved to be negative histologically or disappeared or unchanged on follow-up.

3. Results

53 patients with proven primary malignancy histopathologi-cally (Table 1), were evaluated for suspected osseous metasta-sis using combined PET/CT scans. Metastatic osseous deposits were found in 48 patients, and 5 patients were free from oss-eous metastases.

There were 386 focal lesions in 48 patients evaluated (Table 2). Based on CT and PET/CT, 338 lesions were charac-terized as active metastatic deposits and confirmed histopatho-logically or on follow-up imaging (Fig. 1). PET/CT enabled the retrospective detection of 22 lesions missed on CT (Fig. 2). In 17 focal lesions the CT study was defined as false positive for malignancy, whereas the PET/CT studies were true negative (Fig. 3) as these focal lesions were non-viable (healed

(3)

sclerotic deposits). None of these focal lesions changed or developed activity on 6 months of follow-up. Five lesions are defined as false positive on PET/CT study as they showed active tracer uptake; however, their linear distribution along multiple successive ribs, in a patient with recent history of trauma to the site of uptake confirmed their benign post traumatic nature and the lesions disappeared in the follow-up scan (Fig. 4). The remaining 4 lesions were benign lesions (hemangiomas and bony islands) being negative on both PET/CT and CT studies, and interpreted as true negative.

According to the above data we calculated and compared the performance indices of CT and PET/CT for characterization of 386 lesions in 48 patients (Table 3), as regards sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (Table 3). PET/CT showed sensitivity of 100%, specificity of 80.8%, PPV of 98.6%, NPV of 100%

and accuracy of 98.7% compared with 93.9%, 34.6%, 95.2%, 29% and 89.9%, respectively, for CT data.

4. Discussion

CT is more sensitive than radiology in detection of osseous metastases; however, its usefulness is limited in detecting early bone marrow deposits(7,8). Combined PET/CT images show accurate localization of the active tracer uptake, identify healed osseous deposits, that show absent tracer uptake as well as detect early bone marrow deposits before morphological changes are evident on CT(9).

In our study a total of 386 lesions were analyzed on both CT and PET/CT images to evaluate the sensitivity, specificity and accuracy of each modality and the added value of fused PET/CT in detection of osseous metastases.

The results showed higher sensitivity of PET/CT study than CT study alone (100% and 93.9% respectively). This is explained by the presence of active osseous deposits without structural abnormalities, that were falsely interpreted as negative by CT, and integration of PET improved the CT ability to detect these early marrow based metastases. Also there are no false negative bony lesions detected on PET/CT study. These are matched with the results of previous studies conducted by Nakamato et al. (10), Evangelista et al. (11) and Schaefer et al.(12).

Regarding the specificity, PET/CT also shows higher specificity than CT (80.8% and 34.6% respectively). This is due to presence of false positive lesions on CT study, which were inactive healed osseous metastases. Again, integration of PET remarkably improved the CT specificity in diagnosis of active metastases and identification of those metabolically inert, malignant looking lesions on CT.

Our study results agree with the results of previously done studies conducted by Yang et al. (13) and Liu et al. (14), showing that fused PET/CT improved both CT sensitivity and specificity.

PET/CT sensitivity is higher than its specificity in our study. This is attributed to the presence of few lesions falsely interpreted as positive for metastasis by PET/CT, where there was no abnormality seen on corresponding CT images, and proved to be benign post traumatic changes.

The results of both CT and PET/CT were concordant for most of the lesions (342 lesions out of 386 lesions); however,

Table 1 Total number of cases and their primary malignancy in 53 patients.

No. of cases Primary malignancy

20 Cancer breast

12 Prostatic carcinoma

7 Bronchogenic carcinoma

9 Lymphoma

5 Colonic carcinoma

Table 2 The results of PET/CT, CT, histopathology and/or follow-up for assessment of 386 lesions in 48 patients.

No. of focal lesions PET/CT CT Histopathology and/or follow-up 338 TP TP POSITIVE 22 TP FN POSITIVE 17 TN FP NEGATIVE 4 TN TN NEGATIVE 5 FP TN NEGATIVE

TP: true-positive; TN: true-negative; FP: positive; FN: false-negative.

Fig. 1 81 years old male with history of lung cancer (squamous cell carcinoma), received chemotherapy and referred for status evaluation by PET/CT. (a) CT image shows a large destructive soft tissue mass involving the left sacral ala, interpreted as a metastatic deposit. (b) Corresponding PET/CT image shows that the mass is intensely avid for 18F-FDG with SUV max reaching 20.46, confirming its malignant metastatic nature.

(4)

Fig. 2 42 years old female with history of bilateral breast cancer (invasive ductal carcinoma grade III) underwent bilateral mastectomy followed by chemotherapy and radiotherapy. Presented with elevated tumor marker levels and referred for PET/CT assessment. (a) Axial and sagittal CT image shows no bony abnormalities detected at the scanned bones of axial skeleton, and falsely interpreted as free from metastases. (b) Corresponding PET/CT images show multiple hypermetabolic marrow based focal osseous lesions at left pubic body and dorsolumbar vertebrae with SUV max ranging between 7.5 and 9.7, consistent with true active metastatic deposits.

Fig. 3 43 years old female with history of left breast cancer (invasive ductal carcinoma grade II) metastatic to the bones, referred for assessment by PET/CT study after receiving chemotherapy and radiotherapy. (a) CT image shows a sclerotic lesion at L3 vertebra, falsely interpreted as a malignant sclerotic bony deposit. (b) PET/CT image shows that the lesion is metabolically inert with no any 18F-FDG uptake, denoting its non viable nature (healed sclerotic deposit).

(5)

they were disconcordant for the remaining 44 lesions. When the results were disconcordant, PET/CT was more accurate than CT alone in detection and characterization of the bony lesions and the current study showed that fused PET/CT inter-pretation accuracy is higher than that of CT alone (98.7% and 89.9% respectively).

5. Conclusion

Combined PET/CT improved the CT ability to detect and characterize metastatic osseous deposits, which is essential for proper staging and further management planning. Conflict of interest

The authors declare that there are no conflict of interests. References

(1)Downey SE, Wilson M, Boggis C, et al. Magnetic resonance imaging of bone metastases: a diagnostic and screening technique. Br J Surg 1997;84(8):1093–4. Aug [Medline].

(2)Peh WC. Screening for bone metastases. Am J Orthop 2000;29 (5):405, May [Medline].

(3)Traill ZC, Talbot D, Golding S, Gleeson FV. Magnetic resonance imaging versus radionuclide scintigraphy in screening for bone metastases. Clin Radiol 1999;54(7):448–51, Jul [Medline].

(4)Heindel W, Gu¨bitz R, Vieth V, Weckesser M, et al. The diagnostic imaging of bone metastases. Dtsch Arztebl Int 2014;111:741–7.

(5)Poeppel T, Krause B, Heusner T, Boy C, Bockisch A, Antoch G. PET/CT for the staging and follow-up of patients with malig-nancies. Eur J Radiol 2009;70:382–92.

(6)Zelinka T, Timmers HJ, Kozupa A, et al. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and para-ganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations. Endocr Relat Cancer 2008;15 (1):311–23.

(7)Muindi J, Coombes RC, Golding S, et al. The role of computed tomography in the detection of bone metastases in breast cancer patients. Br J Radiol 1983 Apr;56(664):233–6.

(8)Durning P, Best JJ, Sellwood RA. Recognition of metastatic bone disease in cancer of the breast by computed tomography. Clin Oncol 1983 Dec;9(4):343–6.

(9)Wafaie A, Kassem H, Kotb M, et al. Evaluation of the efficiency of FDG PET/CT in detection and characterization of skeletal metastases. EJRNM 2014;45:181–90.

(10)Nakamoto Y, Cohade C, Tatsumi M, Hammoud D, Wahl RL. CT appearance of bone metastases detected with FDG PET as part of the same PET/CT examination. Radiology 2005;237: 627–34.

(11)Evangelista L, Panunzio A, Polverosi R, Ferretti A, Chondro-giannis S, Pomerri F, et al. Early bone marrow metastasis detection: the additional value of FDG-PET/CT vs. CT imaging. Biomed Pharmacothe 2012;66:448–53.

Fig. 4 57 years old female with history of right renal cell carcinoma, underwent right nephrectomy since 3 years and referred for follow-up PET/CT study; however, she gave history of recent mild trauma to the left side of the back. (a) CT image shows no abnormalities on the ribs. (b) and (c) PET and PET/CT images show metabolically active lesions at posterolateral aspects of the left 8th, 9th and 10th ribs arranged in the same linear axis, confirming their benign post traumatic nature.

Table 3 Comparison of performance indices of CT and PET/CT for characterization of 386 lesions in 48 patients (lesion-based analysis).

No. of lesions TP TN FP FN Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%)

PET/CT 386 360 21 5 0 100 80.8 98.6 100 98.7

CT 386 338 9 17 22 93.9 34.6 95.2 29 89.9

(6)

(12)Schaefer NG, Strobel K, Taverna C, Hany TF. Bone involvement in patients with lymphoma: the role of FDG-PET/CT. Eur J Nucl Med Mol Imag 2007;34:60–7.

(13)Yang HL, Liu T, Wang XM, Xu Y, Deng SM. Diagnosis of bone metastases: a meta-analysis comparing (1)(8)FDG PET, CT, MRI and bone scintigraphy. Eur Radiol 2011;21:2604–17.

(14)Liu N, Ma L, Zhou W, Pang Q, Hu M, Shi F, et al. Bone metastasis in patients with non-small cell lung cancer: the diagnostic role of F-18FDGPET/CT. Eur J Radiol 2010;74:231–5.

References

Related documents

Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata

O percurso feito até aqui permitiu-nos acompanhar as dimensões dialéticas do pensamento adorniano em dois aspectos: 1) na conexão entre progresso e barbárie e o

The combination of theory and real-life tourism and event management case studies provides students with a uniquely engaging and enriching way of learning how Australia is

• Build consumer insight • Educate consumers • Motivate consumers • Deterrence • Renegotiate value Consumer participation in service recovery Perceived fairness:

There are four types of user and social characteristics that affect IS success: attitudes toward technology, enjoyment, trust and user expectations (Petter, DeLone and McLean,

To contribute to this important area of work, this working paper explores property taxation in two secondary cities in Africa: Kisumu (Kenya) and M’Bour (Senegal).. The method used

There were no significant differences due to treatment across the three southern Illinois sites, but at Dixon Springs in 2013, 38-cm rows yielded more than 76-cm rows, and

The development of an academic article within the ResMa IDS program qualifies students to report on the main results of their master thesis research in the form of a