Marcel P.M. Stokkel

18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques

The aim of the present study was to investigate if 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) outperforms conventional imaging techniques for excluding distant metastases prior to neoadjuvant chemotherapy (NAC) treatment in patients with stage II and III breast cancer. Second, we assessed the clinical importance of false positive findings. One hundred and fifty four patients with stage II or III breast cancer, scheduled to receive NAC, underwent an 18F-FDG PET/CT scan and conventional imaging, consisting of bone scintigraphy, ultrasound of the liver, and chest radiography. Suspect additional lesions at staging examination were confirmed by biopsy and histopathology and/or additional imaging. Metastases that were detected within 6xa0months after the PET/CT scan were considered evidence of occult metastasis, missed by staging examination. Forty-two additional distant lesions were seen in 25 patients with PET/CT and could be confirmed in 20 (13%) of 154 patients. PET/CT was false positive for 8 additional lesions (19%) and misclassified the presence of metastatic disease in 5 (3%) of 154 patients. In 16 (80%) of 20 patients, additional lesions were exclusively seen with PET/CT, leading to a change in treatment in 13 (8%) of 154 patients. In 129 patients with a negative staging PET/CT, no metastases developed during the follow-up of 9.0xa0months. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in the detection of additional distant lesions in patients with stage II or III breast cancer are 100, 96, 80, 100, and 97%, respectively. FDG PET/CT is superior to conventional imaging techniques in the detection of distant metastases in patients with untreated stage II or III breast cancer and is associated with a low false positive rate. PET/CT may be of additional value in the staging of breast cancer prior to NAC.

EANM procedure guidelines for therapy of benign thyroid disease

The purpose of the present guidelines on the 131I therapy of benign thyroid disorders formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians on how to treat benign thyroid conditions employing optimal 131I activities. The recommendations were formulated based on recent literature and expert opinion regarding rationale, indications and contraindications for the use of 131I procedures, as well as the adequate 131I activities in different thyroid disorders, and the administration and patient preparation techniques to be used. Recommendations are also provided on history and examinations before 131I therapy, patient counselling and precautions associated with 131I therapy. Furthermore, potential side effects and alternative treatment modalities are reviewed. Special attention is paid to these aspects in the treatment of children undergoing this procedure.

Comprehensive cardiac assessment with multislice computed tomography: evaluation of left ventricular function and perfusion in addition to coronary anatomy in patients with previous myocardial infarction

Objective: To evaluate a comprehensive multislice computed tomography (MSCT) protocol in patients with previous infarction, including assessment of coronary artery stenoses, left ventricular (LV) function and perfusion. Patients and methods: 16-slice MSCT was performed in 21 patients with previous infarction; from the MSCT data, coronary artery stenoses, (regional and global) LV function and perfusion were assessed. Invasive coronary angiography and gated single-photon emission computed tomography (SPECT) served as the reference standards for coronary artery stenoses and LV function/perfusion, respectively. Results: 236 of 241 (98%) coronary artery segments were interpretable on MSCT. The sensitivity and specificity for detection of stenoses were 91% and 97%. Pearson’s correlation showed excellent agreement for assessment of LV ejection fraction between MSCT and SPECT (49 (13)% v 53 (12)%, respectively, r u200a=u200a 0.85). Agreement for assessment of regional wall motion was excellent (92%, κ u200a=u200a 0.77). In 68 of 73 (93%) segments, MSCT correctly identified a perfusion defect as compared with SPECT, whereas the absence of perfusion defects was correctly detected in 277 of 284 (98%) segments. Conclusions: MSCT permits accurate, non-invasive assessment of coronary artery stenoses, LV function and perfusion in patients with previous infarction. All parameters can be assessed from a single dataset.

Heading toward radioactive seed localization in non-palpable breast cancer surgery? A meta-analysis.

Wire‐guided localization is the most commonly used technique for intraoperative localization of non‐palpable breast cancer. Radioactive seed localization (RSL) is becoming more popular and seems to be a reliable alternative for intraoperative lesion localization. The purpose of the present meta‐analysis was to evaluate the use of RSL. Primary study outcomes were irradicality and re‐excision rates. In total 3168 patients were included. The clinical adaptation shows growing confidence in RSL and further growth is expected. J. Surg. Oncol. 2015 111:185–191.

Increasing importance of 18F-FDG PET in the diagnosis of neurolymphomatosis

Neurolymphomatosis (NL) is a rare clinical entity that is defined as infiltration of the nervous system by a known or unknown haematological malignancy and is difficult to diagnose. Fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging is increasingly being used in haematological malignancies. This article focusses on the role of 18F-FDG PET in the diagnosis and management of NL by presenting a review of cases described in the literature. Reports on NL that used PET with or without computed tomography (CT) as a diagnostic modality were extracted from Medline and evaluated. A total of 58 patients described in 49 case reports on NL were found. In 36 distinctive patients 18F-FDG PET with or without CT was used as a diagnostic modality. In 91% of patients PET showed uptake in various structures in the central or peripheral nervous system, suggesting involvement of lymphoma. Predilection localizations were the brachial and lumbar plexuses, along the course of peripheral nerves of the extremities, and the trigeminal nerve root. MRI, cerebrospinal fluid or bone marrow analysis were frequently negative. In the cases described in the literature 18F-FDG PET assisted in diagnosing NL by providing a whole-body evaluation, showing frequent uptake in affected nervous structures and supported disease management by defining a target for biopsy, monitoring progression and evaluating response to treatment. As other diagnostic methods may be negative, the importance of PET-CT is increasing in the diagnosis and management of this rare clinical entity.

FDG-avid sclerotic bone metastases in breast cancer patients : a PET/CT case series

Distant metastases from breast cancer most frequently occur in the skeleton. Although 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), with or without computed tomography (CT), is superior to bone scintigraphy for the detection of osteolytic bone metastases, it has been reported that sclerotic bone metastases frequently show no or only a low degree of FDG uptake on PET and PET/CT. Since both lytic and sclerotic metastases can occur in breast cancer patients, bone scintigraphy may remain of additional value in these patients. In this case series, we describe four breast cancer patients in whom FDG PET/CT has clearly visualized sclerotic bone metastases because of increased FDG uptake. Not so much the type of metastasis (sclerotic or lytic), but possibly the characteristics of the primary tumor or treatments prior to the FDG PET/CT scan might influence the degree of FDG uptake of bone metastases. The ability to detect sclerotic bone metastases based on increased FDG uptake supports the use of FDG PET/CT as a staging procedure in breast cancer patients, but knowledge of factors determining the visibility of bone metastases with FDG PET/CT is crucial.

124I PET/CT to predict the outcome of blind 131I treatment in patients with biochemical recurrence of differentiated thyroid cancer; results of a multicenter diagnostic cohort study (THYROPET)

Patients with suspected recurrence from differentiated thyroid carcinoma, based on an increased thyroglobulin (Tg) level and negative neck ultrasound (US), pose a clinical dilemma. Because standard imaging has a low yield identifying potential recurrence, blind 131I treatment is often applied. However, a tumor-negative 131I whole-body scintigraphy (WBS) prevails in 38%–50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that 124I PET/CT can identify the patients with a tumor-negative posttherapy 131I WBS. Methods: Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for blind 131I therapy. All patients underwent 124I PET/CT after administration of recombinant human thyroid-stimulating hormone. Subsequently, after 4–6 wk of thyroid hormone withdrawal patients were treated with 5.5–7.4 GBq of 131I, followed by WBS a week later. The primary endpoint was the number of 131I therapies that could have been omitted using the predicted outcome of the 124I PET/CT, operationalized as the concordance of tumor detection by 124I PET/CT, using post-131I therapy WBS as the reference test. The study would be terminated if 3 patients had a negative 124I PET/CT and a positive posttherapy 131I scan. Results: After inclusion of 17 patients, we terminated the study preliminarily because the stopping rule had been met. Median Tg level at 131I therapy was 28 μg/L (interquartile range, 129). Eight posttherapy WBS were negative (47%), all of which were correctly predicted by negative 124I PET/CT. Nine posttherapy WBS showed iodine-avid tumor, of which 4 also had positive 124I PET/CT findings. Sensitivity, specificity, negative predictive value, and positive predictive value of 124I PET/CT were 44% (confidence interval [CI], 14%–79%), 100% (CI, 63%–100%), 62% (CI, 32%–86%), and 100% (CI, 40%–100%), respectively. Implementation of 124I PET in this setting would have led to 47% (8/17) less futile 131I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy. Conclusion: In patients with biochemical evidence of recurrent differentiated thyroid carcinoma and a tumor-negative neck US, the high false-negative rate of 124I PET/CT after recombinant human thyroid-stimulating hormone 124I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind 131I therapy.

Differences in the Biologic Activity of 2 Novel MEK Inhibitors Revealed by 18F-FDG PET: Analysis of Imaging Data from 2 Phase I Trials

Two mitogen-activated protein kinase kinase (MAPK2, also known as MEK) inhibitors were assessed with 18F-FDG PET in separate phase I clinical studies, clearly illustrating the potential of metabolic imaging for dose, dosing regimen, and compound selection in early-phase trials and utility for predicting nonresponding patients. Methods: 18F-FDG PET data were collected during 2 independent, phase I, dose-escalation trials of 2 novel MEK inhibitors (RO5126766 and RO4987655). PET acquisition procedures were standardized between the 2 trials, and PET images were analyzed centrally. Imaging was performed at baseline; at cycle 1, day 15; and at cycle 3, day 1. A 10-mm-diameter region of interest was defined for up to 5 lesions, and peak standardized uptake values were determined for each lesion. The relationship between PET response and pharmacokinetic factors (dose and exposure), inhibition of extracellular-signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells, and anatomic tumor response as measured by Response Evaluation Criteria in Solid Tumors was investigated for both compounds. Results: Seventy-six patients underwent PET, and 205 individual PET scans were analyzed. Strong evidence of biologic activity was seen as early as cycle 1, day 15, for both compounds. 18F-FDG PET revealed striking differences between the 2 MEK inhibitors at their recommended dose for phase II investigation. The mean amplitude of the decrease in 18F-FDG from baseline to cycle 1, day 15, was greater for patients receiving RO4987655 than for those receiving RO5126766 (47% vs. 16%, respectively; P = 0.052). Furthermore, a more pronounced relationship was seen between the change in 18F-FDG uptake and dose or exposure and phosphorylated ERK inhibition in peripheral blood mononuclear cells in patients receiving RO4987655. For both investigational drugs, PET responses tended to be greatest in patients with melanoma tumors. 18F-FDG was able to identify early nonresponding patients with a 97% negative predictive value. Conclusion: These data exemplify the role of 18F-FDG PET for guiding the selection of novel investigational drugs, choosing dose in early-phase clinical development, and predicting nonresponding patients early in treatment.

Recurrent differentiated thyroid cancer: towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): study protocol of a multicenter observational cohort study

BackgroundAfter initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated blindly with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.Methods/DesignIn a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for ‘blind’ therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.DiscussionThis study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.Trial registrationClinicaltrials.gov identifier: NCT01641679

Assessment of global cardiac I-123 MIBG uptake and washout using volumetric quantification of SPECT acquisitions.

BackgroundAssessment of cardiac innervation using single-photon emission computer tomography (SPECT) is less established than planar imaging, but may be more suitable for quantification. Therefore, a volumetric quantification of I-123 MIBG SPECT acquisitions was performed. Reproducibility, the effects of extra cardiac I-123 MIBG uptake and the relation with conventional planar indices were evaluated.Methods54 patients referred for planar and SPECT I-123 MIBG acquisitions were included. Ellipsoidal or box-shaped volumes of interest were placed on the left ventricle, cardiac lumen, mediastinum, lung and liver. SPECT segmentation was performed twice in all patients. Indices were determined based on the heart-to-mediastinum (HM), myocardial wall-to-mediastinum and myocardial wall-to-lumen regions. HM ratios and washout rates were also determined based on anterior planar images.ResultsCardiac count densities were highly reproducible (CV 1.5-5.4, ICC 0.96-0.99) and inter-rater variability was low (CV 1.8-6.8, ICC 0.94-0.99). Mediastinal uptake was an important explanatory variable of uptake in the entire heart (early R2xa0=xa00.36; delayed R2 =0.43) and myocardial wall (early R2xa0=xa00.28; delayed R2xa0=xa00.37). Lung washout was an explanatory variable of organ washout of the heart (heart R2xa0=xa00.38; myocardial wall R2xa0=xa00.33). In general, SPECT indices showed moderate-to-good correlations with the planar uptake (PCC 0.497-0.851).ConclusionBy applying a volumetric segmentation method we were able to segment the heart in all patients. SPECT I-123 MIBG quantification was found to be highly reproducible and had a moderate to good correlation with the planar indices.