Japanese Journal of Clinical Oncology 32:244-247 (2002)
© 2002 Foundation for Promotion of Cancer Research
Clinical Impact of [18F]FDG-PET in Patients with Suspected Recurrent Breast Cancer Based on Asymptomatically Elevated Tumor Marker Serum Levels: a Preliminary Report
Departments of 1 Family Medicine and 4 Nuclear Medicine, China Medical College Hospital, Taichung, 2 Department of Nuclear Medicine and PET Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei and 3 Department of Nuclear Medicine and PET Center, National Taiwan University Hospital, Taipei, Taiwan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective: To evaluate retrospectively the impact of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) on the detection of recurrent breast cancer based on asymptomatically elevated tumor markers levels.
Methods: Whole-body FDG-PET was performed in 30 patients with suspected recurrent breast cancer and asymptomatic tumor marker increase but negative or equivocal other imaging modality results. A blood sample was drawn in each case for marker assay (CA 15-3 and CEA) on the same day as the FDG-PET. All of these 30 asymptomatic patients had either CA l5-3 >32 U/ml or CEA >5 ng/ml. The final diagnosis of recurrent breast cancer was established by operation/biopsy histopathological findings or clinical follow-up for >1 year by additional morphological imaging techniques.
Results: Among the 30 patients, the final diagnosis of recurrent breast cancer was established in 38 sites in 28 patients. FDG-PET accurately detected 35/38 sites in 25/28 patients with recurrence. The diagnostic sensitivity and accuracy of FDG-PET in patients with suspected recurrent breast cancer and asymptomatically elevated tumor markers were 96 and 90%, respectively.
Conclusions: FDG-PET is a useful technique for detecting recurrent breast cancer suspected from asymptomatically elevated tumor markers levels and has an important clinical impact on the management of these patients.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Tumor markers whose blood levels seem to correlate with the tumor mass are useful tools in the detection and/or follow-up of certain cancers. However, they lack specificity and elevation of their levels, although very suggestive, does not always prove the presence or recurrence of cancer and does not predict the number and localization of tumor sites. In current clinical practice, patients regularly undergo a number of clinical examinations for post-operative follow-up. Carcinoembryonic antigen (CEA) and cancer-antigen 15-3 (CA 15-3) are the most frequently used tumor markers for the detection of asymptomatic recurrences of breast cancers (1,2).
[18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) has been introduced as a promising technique for the primary detection and follow-up of many tumors, including breast cancer (3–7). It is unquestioned that early detection of recurrence breast cancer has a significant influence on therapy. Local and axillary lymph node (LN) recurrence would be treated by surgical revision and often radiation, while mediastinal LN (lung, liver, bone) recurrence would require chemotherapy and/or radiotherapy (8). Therefore, we retrospectively evaluated the impact of FDG-PET on the detection of recurrent breast cancer based on asymptomatically elevated tumor markers levels.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients’ Characteristics
Thirty female patients (from 38 to 65 years old) with breast cancer after treatment who were suspected of recurrence based on asymptomatically elevated tumor markers’ levels were enrolled in this study (Table 1). The final diagnosis of recurrent breast cancer was established by operation/biopsy histopathological findings or clinical follow-up for >1 year by additional morphological imaging techniques.
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Imaging Modality Surveys
All of the 30 patients received imaging modality surveys including technetium-99m methylene diphosphonate (Tc-99m MDP) whole-body bone scan, ultrasonography of breasts, mammography and computed tomography of the chest and abdomen. All of their results were negative or equivocal. Tc-99m MDP whole-body bone scans were obtained with a large field-of-view, dual-head gamma camera (Helix HR, Elscint, Haifa, Israel) fitted with a general-purpose collimator (low energy, medium sensitivity and resolution). Anterior and posterior whole-body images (1–1.2 million counts) were acquired 2–3 h after the intravenous administration of 25 mCi (925 MBq) of Tc-99m MDP. Ultrasonography of breasts was performed with an Aloka 650 instrument (Aloka, Tokyo, Japan) with a high-resolution (7.5 MHz) mechanical sector probe. The patients were placed in the supine oblique position with the side to be examined raised slightly to distribute the breast tissue evenly over the pectoral muscle. The ipsilateral arm was raised to tense the breast as much as possible. Scans were obtained both transversely and longitudinally, taking special care to examine the periphery to avoid missing any occult lesions. Mammography was performed using a mammography unit (Bennett M-CTR BMC 28195 M-145 95480–05, 100 kHz) with Kodak Min-R 2000 film in standard craniocaudal and mediolateral projections and, if necessary, oblique and axillary tail views. Computed tomography (CT) of the chest and abdomen was performed in the axial and coronal planes after the intravenous injection of contrast medium. CT scans were obtained with a Somaton DRH CT scanner (Siemens, Erlangen, Germany) with an axial section thickness of 5 mm.
Whole-body FDG-PET Study
All the patients fasted for more than 4 h before the whole-body PET study. A 10 mCi (370 MBq) dose of FDG was administered intravenously 30–45 min before imaging. The whole-body PET examination was performed with a CTI-Siemens ECAT HR+ scanner (CTI, Knoxville, TN). This whole-body, high-resolution PET allows simultaneous imaging of 47–63 transaxial slices in the two-dimensional (2D) mode in a 15 cm axial field-of-view (FOV). In the 2D acquisition mode (septa extended), the nominal tomographic resolution is ~5 mm full width at half-maximum (FWHM) and the axial resolution is ~4 mm at the FOV center. Seven or eight overlapping emission scans (according to the body length) of 7 min each were obtained from the bladder level towards the head. Data were acquired in 2D true coincidence mode. Transmission scans of 3 min each were then acquired following each emission scan. Transmission scans were performed in the 2D mode, using three rotating germanium-68 rod sources, combined with the rod windowing technique. The total scan duration was 70 min. Positive FDG-PET findings were defined as a focus of increased FDG uptake, above the intensity of surrounding normal tissue activity, excluding the physiologically increased FDG uptake areas of renal pelvis, urinary bladder, bowel, myocardium and brain. All FDG-PET images were evaluated primarily by visual interpretation of the agreement of at least two of three experienced nuclear medicine physicians who were not blinded to available data. When the two reviewers did not agree, they reviewed the images together to reach a consensus; in this study, there were two instances of disagreement concerning FDG-PET images.
Tumor Markers
In all of the 30 patients, a blood sample was drawn for marker assay on the same day as the FDG-PET. Both CEA and CA 15-3 were measured with immunoradiometric assay (IRMA ELSA 2-CEA and ELSA CA 15-3, CIS Bio International, France). The sensitivity of the CA 15-3 and CEA assays were 0.2 U/ml and 0.3 ng/ml, respectively, with inter- and intra-assay coefficients of variation (CV) of <10%. Serum samples were collected prior to the injection of FDG for imaging and stored at –20°C before the analysis was performed. Normal controls were 78 healthy subjects whose age ranged from 35–72 years. The mean CA 15-3 level was 15.7 ± 5.5 U/ml (mean ± standard deviation, SD) with 99% of the values below 32 U/ml. We therefore used 32 U/ml of CA 15-3 as a cut-off value. The mean CEA level was 1.75 ± 0.93 ng/ml (mean ± SD) with 100% of the values below 5 ng/ml. The cut-off value for CEA was therefore 5 ng/ml.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Of the total 30 patients, two did not have recurrent lesions. Among the other 28 patients who had recurrent lesions (22 ductal, three lobular and three other carcinomas), 14 had local recurrences, 12 had axillary lymph node recurrences and nine had distal recurrent lesions (Fig. 1). False-negative FDG-PET findings missed one distal (mediastinal LN) recurrence in one patient developed 6 months after a negative FDG-PET. False-positive FDG PET findings corresponded to two cases with local soft tissue and distal lung infections (Fig. 2). The diagnostic sensitivity and accuracy of FDG-PET in patients with suspected recurrent breast cancer and asymptomatically elevated tumor markers were 96 and 90%, respectively.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The sensitivity of the elevated serum CA15-3 level increased with disease stage and was better correlated than serum CEA. Therefore, the clinical usefulness of serum tumor markers in the monitoring of therapeutic interventions is high, and they also permit early detection of local recurrence and metastasis (9–11). Employing a tumor marker level as a guide to the performance of FDG-PET necessarily entails the setting of a decision-making threshold. In the present study, the normal upper value adopted by our laboratory (CA 15-3 <32 U/ml or CEA <5 ng/ml) was arbitrarily retained as the threshold for FDG-PET to rule out recurrent breast cancer.
The diagnostic sensitivity and accuracy of FDG-PET in patients with suspected recurrent breast cancer and asymptomatically elevated tumor markers were 96 and 90%, respectively. Therefore, our results suggested FDG-PET is very useful for detecting recurrent breast cancer with asymptomatically elevated tumor markers. One false-positive case in the detection of local recurrence was due to infection on the chest wall soft tissue (cellulites) and the other false-positive case in the detection of distal metastasis was due to lung infection (tuberculosis) (Fig. 2). Increased FDG uptake in the inflammatory areas or infection lesions is not uncommon because the glycolytic metabolism is elevated in the leukocytic infiltration associated with inflammatory processes (12–14). There was a false-negative case with distal (mediastinal LN) metastasis in this study. We considered micrometastasis to be responsible for this false-negative case. According to the literature, some patients have micrometastatic disease only and will therefore show false-negative FDG-PET results for LN involvement, although patients with micrometastatic disease often also have macroscopic metastases (15,16).
These preliminary results suggest that FDG-PET is a useful technique for detecting recurrent breast cancer suspected from asymptomatically elevated tumor markers’ levels and negative or equivocal other imaging modality results. FDG-PET has an important clinical impact on the management of these patients.
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FOOTNOTES |
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+ For reprints and all correspondence: Chia-Hung Kao, Department of Nuclear Medicine and PET Center, China Medical College Hospital, 2 Yuh-Der Road, Taichung 404, Taiwan. E-mail: d10040@hpd.cmch.org.tw
Abbreviations: FDG-PET, [18F]fluorodeoxyglucose positron emission tomography; CEA, carcinoembryonic antigen; CA 15-3, cancer-antigen 15-3; LN, lymph node
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Received February 12, 2002; accepted April 19, 2002
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