Holger Schirrmeister

Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures.

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.

Early Detection and Accurate Description of Extent of Metastatic Bone Disease in Breast Cancer With Fluoride Ion and Positron Emission Tomography

PURPOSE Previous studies have shown that bone metastases are revealed by magnetic resonance imaging (MRI) or bone marrow scintigraphy several months before they are visible by conventional bone scintigraphy (BS). We present a new approach for detecting bone metastases in patients with breast cancer. We compared findings obtained with fluoride ion (F-18) and positron emission tomography (PET) with those obtained with conventional BS. PATIENTS AND METHODS Thirty-four breast cancer patients were prospectively examined using F-18-PET and conventional BS. F-18-PET and BS were performed within 3 weeks of each other. Metastatic bone disease was previously known to be present in six patients and was suspected (bone pain or increasing levels of tumor markers, Ca(2+), alkaline phosphatase) in 28 patients. Both imaging modalities were compared by patient-by-patient analysis and lesion-by-lesion analysis, using a five-point scale for receiver operating characteristic (ROC) curve analysis. A panel of reference methods was used, including MRI (28 patients), planar x-ray (17 patients), and spiral computed tomography (four patients). RESULTS With F-18-PET, 64 bone metastases were detected in 17 patients. Only 29 metastases were detected in 11 patients with BS. As a result of F-18-PET imaging, clinical management was changed in four patients (11.7%). For F-18-PET, the area under the ROC curve was 0.99 on a lesion basis (for BS, it was 0.74; P <.05) and 1.00 on a patient basis (for BS, it was 0.82; P <.05). CONCLUSION F-18-PET demonstrates a very early bone reaction when small bone marrow metastases are present, allowing accurate detection of breast cancer bone metastases. This accurate detection has a significant effect on clinical management, compared with the effect on management brought about by detection with conventional BS.

FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters

Abstract. The aim of this study was to evaluate the possible correlation between preoperative FDG-PET results in human breast cancer and the prognostic markers Ki-67, c-erb B2, p53, oestrogen/progesterone receptor status, axillary lymph node status, tumour size and tumour grading. Seventy-five female patients with breast cancer were included in this prospective study. Patient selection was independent of tumour size and the suspected clinical stage of disease. A high-resolution full-ring scanner (Siemens ECAT HR+) was used for PET imaging. The FDG uptake of breast tumours was calculated as the tumour to background ratio (TBR). In resected cancer tissue specimens, the proliferative fraction was evaluated by Ki-67 immunostaining. Additionally, immunostaining of the prognostic markers c-erb B2, p53, and progesterone and oestrogen receptors was performed. Haematoxylin and eosin-stained sections were used for tumour grading. Correlations between FDG uptake and prognostic markers were assumed to be significant at P<0.05 using the Mann-Whitney U test. In ductal breast cancer, mean TBR was 17.3 (median 7.7, range 1.6–122.7), while in lobular cancer it was 6.5 (median 3.7, range 1.4–22.7). Mean proliferative fraction (% Ki-67 positive tumour cells) was 15%±13.8% (median 10%, range 0%–60%). Twenty-three carcinomas showed <5% Ki-67 positive tumour cells. Statistical analysis indicated a positive correlation between FDG uptake and proliferative index in ductal breast cancer (P<0.0001, r=0.63). By contrast, there was no correlation between FDG uptake and c-erb B2 (P=0.79), p53 (P=0.92), tumour grading (P=0.09), oestrogen receptor status (P=0.41), progesterone receptor status (P=0.34), axillary lymph node status (P=0.90) and tumour size (P=0.3). It is concluded that FDG uptake is significantly higher in ductal breast cancer than in lobular cancer (P<0.05). FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining (P<0.05). A significant correlation with the other prognostic markers, however, could not be demonstrated.

Initial results in the assessment of multiple myeloma using 18F-FDG PET.

Abstract. This prospective study was undertaken to investigate the appearance of multiple myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient management were evaluated. Forty-three patients with known multiple myeloma (n=28) or solitary plasmacytoma (n=15) underwent FDG-PET. The results of routinely performed radiographs and of scans obtained using all available imaging modalities (MRI, CT), as well as the clinical course, were used for verification of detected lesions. Focally increased tracer uptake was observed in 38 of 41 known osteolytic bone lesions (sensitivity 92.7%) in 23 patients. In addition, 71 further bone lesions which were negative on radiographs were detected in 14 patients. Twenty-six (36.6%) of these lesions could be confirmed in ten patients. As a result of FDG-PET imaging, clinical management was influenced in five (14.0%) patients. The positive predictive value for active disease was 100% in patients with focal or mixed focal/diffuse skeletal FDG uptake and 75% in patients with diffuse bone marrow uptake. Depending on the interpretation of the PET scans in patients with diffuse bone marrow uptake, the sensitivity ranged from 83.8% to 91.9% and the specificity from 83.3% to 100%. FDG-PET thus proved highly accurate in detecting multiple myeloma, and revealed a greater extent of disease than routine radiographs in 14 of 23 (60.9%) patients who had osteolytic bone lesions. FDG-PET might contribute to the initial staging of solitary plasmacytoma.

F-18 NaF PET for Detection of Bone Metastases in Lung Cancer: Accuracy, Cost-Effectiveness, and Impact on Patient Management†

As bone metastases might be present in lung cancer despite a normal bone scan, we examined various alternatives prospectively. Positron emission tomography using F‐18 sodium fluoride (PET) and single photon emission tomography (SPECT) were more sensitive than a planar bone scan. PET was more accurate with a shorter examination time than SPECT but had higher incremental costs.

Is 18F-fluorodeoxyglucose positron emission tomography in recurrent colorectal cancer a contribution to surgical decision making?

Abstract Background: Accuracy of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contribution to surgical decision making in recurrent or metastatic colorectal cancer were evaluated. Methods: One hundred whole-body PET tests in colorectal cancer patients (1994 to 1998) were compared with computed tomography (CT), liver ultrasonography, and carcinoembryonic antigen (CEA) test. Mean follow-up was 12 months. Results: Sensitivity, specificity, and accuracy of FDG-PET for malignant findings were, respectively, 98%, 90% and 95%; for 87 CT scans, 91%, 72%, and 82%; for 98 CEA tests, 76%, 90%, and 82%; for detection of liver metastases with PET, 100%, 99%, and 99%; and for 68 ultrasound tests, 87%, 96%, and 93%. PET accuracy for local recurrence was 96%. Additional information was provided by PET in 86% of cases (abdomen, thorax, liver). PET influenced surgical decisions in 61% of cases. Conclusion: FDG-PET adds relevant accuracy to the conventional staging of patients with colorectal cancer and may cost-effectively help to select the appropriate treatment.

Dissociating a Common Working Memory Network from Different Neural Substrates of Phonological and Spatial Stimulus Processing

Positron emission tomography was used to investigate common versus specific cortical regions for the maintenance of spatial versus phonological information in working memory (WM). Group and single-subject analyses of regional cerebral blood flow during a new 2 x 2 factorial n-back task were performed. Eight subjects had to memorize either phonological features or the location of serially presented syllables. Brain activation during phonological judgment and spatial judgment (0-back) was compared with that during two corresponding WM conditions (2-back). We observed a common network associated with the requirement of maintaining and sequencing items in WM. Seven or more subjects activated (posterior) superior frontal sulcus (pSFS, BA 6/8, global maximum) and/or adjacent gyri, posterior parietal cortex, and precuneus (BA 7). Less consistently, bilateral middle frontal gyrus (BA 9/46) was involved. Bilateral anterior (BA 39/40) and posterior (BA 7) intraparietal sulcus, as well as right pSFS, exhibited dominance for spatial WM. Although underlying stimulus processing pathways for both types of information were different, no region specific for phonological WM was found. Robust activation within the left inferior frontal gyrus (BA 44 and 45) was present, during both phonological WM and phonological judgment. We conclude that the controversial left prefrontal lateralization for verbal WM reflects more general phonological processing strategies, not necessarily required by tasks using letters. We propose a stimulus-independent role for the bilateral pSFS and its vicinity for maintenance and manipulation of different context-dependent information within working memory.

Positron emission tomography (PET) for staging of solitary plasmacytoma.

PURPOSE This study was undertaken to investigate the clinical value in staging patients with plasmacytoma (PC) using positron emission tomography (PET). METHODS Fifteen patients with known PC underwent PET using F-18 fluorodeoxyglucose (FDG-PET). FDG-PET was done for staging in 11 patients and for restaging in 4 patients. Eleven patients had PC of bone, and 4 patients had extramedullary PC. The results of all available imaging modalities, such as x-ray, magnetic resonance imaging (MRI), computed tomography (CT), bone scans, and of the clinical course, were used for verification of detected lesions. RESULTS Intensively increased tracer uptake was observed in 9 of 11 patients with bone lesions. One osteolytic lesion showed only slightly increased FDG-uptake and another PC of a rib (30 mm diameter) presented without FDG-uptake. The four extramedullary PC showed an intensively increased tracer uptake. In addition, 20 (10 confirmed) further plasmacytoma lesions, which were negative on the standard staging methods, were detected in 4 patients (27%). Since the diagnosis was changed from PC to multiple myeloma, a potentially curative local therapy was changed to a palliative systemic therapy. CONCLUSION Although FDG-PET was false negative in 1 patient (7%) and indeterminate in another patient, additional lesions were detected in 5 (33%) of the patients, resulting in a change in the therapy regimen in 4 (27%) of the 15 patients.

Biological characterisation of breast cancer by means of PET

Breast cancer is associated with increased glucose consumption and can therefore be visualised with the glucose analogue [18F]2-deoxy-2-fluoro-d-glucose (FDG) and positron emission tomography (PET). FDG uptake in the primary tumour can vary substantially, and specific tumour characteristics have been demonstrated to determine the degree of glucose metabolism. Factors with a major influence on FDG uptake in breast cancer comprise expression of glucose transporter Glut-1 and hexokinase I, number of viable tumour cells per volume, histological subtype, tumour grading, microvessel density and proliferative activity. Recently, an association between high FDG uptake and a worse prognosis was suggested. Several studies have been performed correlating FDG uptake with a variety of prognostic and molecular biomarkers as well as parameters predicting tumour response to therapy. However, a correlation with important clinical prognostic markers such as axillary lymph node status and size of the primary tumour, expression of oestrogen and progesterone receptors, proto-oncogene c-erbB-2 or VEGF could not be demonstrated. The lack of correlation with important markers of prognosis does not suggest that FDG uptake might be used as a prognostic criterion in breast cancer. Innovative radiotracers for specific imaging of tumoural perfusion ([15O]H2O), hormone receptor expression ([18F]FES), protein synthesis ([11C]methionine), proliferation rate ([18F]FLT) or bone mineralisation ([18F]fluoride) may provide additional information compared with that provided by FDG PET.

Anatomical distribution and sclerotic activity of bone metastases from thyroid cancer assessed with F-18 sodium fluoride positron emission tomography.

Currently, bone scintigraphy (BS) is considered to lack sensitivity in detecting bone metastases (BM) from thyroid cancer. We evaluated the anatomical distribution and metabolic behavior of BM as well as the accuracy of BS with and without combination of whole-body iodine scintigraphy (WBI) in detecting metastatic bone disease in thyroid carcinoma. F-18 positron emission tomography (PET), x-ray, BS, and WBI were performed in 35 patients with known or suspected bone metastases from papillary (9 patients) or follicular (26 patients) thyroid carcinoma. Twenty-two metastases were previously known in 14 patients. The indication was staging in 21 patients with high risk for BM, elevated thyroglobulin (Tg)-levels or evaluation of exact extent of BM (14 patients). In addition, results of WBI (35 patients), X-ray (35 patients) F-18 PET (35 patients), MRI of the spine (13 patients), and FDG-PET (15 patients) as well as the clinical course (1.5-4 years) were correlated. BM were detected in 18 patients. Solitary, bifocal, or multiple lesions were present in 9, 2, and 7 patients, respectively. The anatomical distribution of BM (n = 43) was as follows: spine, 42%; skull, 2%; thorax, 16%; femur, 9%; pelvis, 26%; humerus and clavicle, 5%. Sensitivity of BS in interpreting patients as positive or negative for having BM was 64%-85% (specificity, 95%-81%). The combination of BS and WBI was 100% sensitive in detecting metastatic bone disease. One patient had a single BM that was positive at BS but negative on WBI. All metastases were osteolytic on x-ray and two-thirds presented a missing or very limited osteosclerotic bone reaction on F-18 PET. Our data confirm the limited sensitivity of planar BS in detecting BM from thyroid cancer. The combination of BS and WBI, however, was highly accurate. Compared to other malignancies, the distribution pattern of BM presented a lower percentage of vertebral metastases and more patients with single metastases. Those findings in combination with a missing or only slight osteosclerotic bone reaction explain the limited sensitivity of planar BS alone.