Jeroen Mertens

Value of DCE-MRI and FDG-PET/CT in the prediction of response to preoperative chemotherapy with bevacizumab for colorectal liver metastases

Background:The purpose of this study was to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET/CT) for evaluation of response to chemotherapy and bevacizumab and for prediction of progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) with potentially resectable liver lesions.Methods:A total of 19 mCRC patients were treated with FOLFOX/FOLFIRI and bevacizumab followed by surgery. Dynamic contrast-enhanced magnetic resonance imaging and FDG-PET/CT were performed before treatment and after cycle 5. PET results were quantified by calculating maximum standardised uptake value (SUVmax) whereas area under the enhancement curve (AUC), initial AUC (iAUC) and the endothelial transfer constant (Ktrans) were used to quantify DCE-MRI. Pathological analysis of the resection specimen was performed, including measurement of microvessel density (MVD) and proliferation index.Results:Both AUC and iAUC were significantly decreased following bevacizumab therapy (median change of 22% (P=0.002) and 40% (P=0.001) for AUC and iAUC, respectively). Progression-free survival benefit was shown for patients with >40% reduction in Ktrans (P=0.019). In the group of radiological responders, the median baseline SUVmax was 3.77 (IQR: 2.88–5.60) compared with 7.20 (IQR: 4.67–8.73) in nonresponders (P=0.021). A higher follow-up SUVmax was correlated with worse PFS (P=0.012). Median MVD was 10.9. Progression-free survival was significantly shorter in patients with an MVD greater than 10, compared with patients with lower MVD (10 months compared with 16 months, P=0.016).Conclusion:High relative decrease in Ktrans, low follow-up SUVmax and low MVD are favourable prognostic factors for mCRC patients treated with bevacizumab before surgery.

99mTc-labelled macroaggregated albumin (MAA) scintigraphy for planning treatment with 90Y microspheres

Purpose90Y microspheres are used for intra-arterial treatment of liver tumours. In the patient preparation, a hepatic angiogram is performed and all arteries that could transport microspheres from the targeted liver vasculature to extrahepatic organs are blocked. 99mTc-labelled macroaggregated albumin (MAA) is injected intra-arterially to simulate the treatment and whole-body scintigraphy and single photon emission computed tomography (SPECT) of the abdomen are performed.MethodsVarious aspects of lung shunt fraction (LSF) estimation were studied: interobserver and intrapatient variability, influence of scan quality and underlying disease. Secondly, the interobserver variability in reading the MAA SPECT of the abdomen was investigated. We reviewed 90 whole-body scans and 20 SPECT scans performed at our institution. Readers were blinded to each other’s findings. Scoring the scan quality was based on the visualization of tracer degradation.ResultsThe mean difference in LSF between the readers was 1%. In 1 of 23 patients who underwent repeated MAA injections a marked change in LSF was observed. No significant differences in LSF were recorded for primary versus secondary liver tumours. There was a correlation between scan quality and LSF, suggesting that low scan quality leads to overestimation of the LSF. Concordant results in ruling out the presence of extrahepatic tracer deposition were reached in 17 of 20 scans (85%).ConclusionInterobserver and intrapatient variability in LSF calculation was limited. LSF was clearly dependent on scan quality. The underlying disease had no significant impact on the LSF. Interobserver variability for reading the MAA SPECT scans was acceptable.

Tumor perfusion using first-pass F-18 FDG PET images.

Many reports in the literature have focused on FDG PET imaging at conventional (60 minutes after injection) or delayed (several hours after injection) intervals, which exploits increased glycolysis in tumors for diagnosis. However, in rapidly growing tumors, accelerated glycolysis is, among other factors, mediated by hypoxia and poor perfusion. Interestingly, first-pass (0-2 minutes after injection) FDG PET images were shown to provide an index of perfusion. Here, we illustrate that tracer uptake by various (parts of) tumors is discrepant between first-pass and conventional PET images, probably reflecting the direct control of glucose transporter overexpression by hypoxia, resulting from poor perfusion (Warburgs hypothesis).

Scapular osteomyelitis as a rare complication of Staphylococcus aureus endocarditis bone scintigraphy findings

Spondylodiscitis and septic arthritis of the large joints are well-known complications of infective endocarditis. In contrast, osteomyelitis of the appendicular skeleton as a complication of infective endocarditis has not yet well been established in the medical literature. We report a case of scapular osteomyelitis in a 27-year-old woman with Staphylococcus aureus endocarditis, which was detected by 3-phase Tc-99m MDP bone scintigraphy. Although the initial complaint of the patient was right shoulder pain, there was a significant delay in diagnosis, because the initial conventional radiograph was negative.

An evaluation of FDG-PET as a predictor of metabolic response to chemotherapy in metastatic colorectal cancer patients (mCRC)

e14057 Background: Limited information is available on the role of FDG-PET in the management of patients with mCRC. Bevacizumab prolongs overall survival and progression-free survival (PFS) when added to standard chemotherapy in mCRC patients. The purpose of the study was to explore the possible role of FDG-PET as response predictor for bevacizumab treatment in liver mCRC patients. METHODS Eighteen mCRC patients (7 women and 11 men), were treated with FOLFOX (n=12) or FOLFIRI (n=6) and bevacizumab (5 mg/kg). FDG-PET scans were performed before treatment (baseline) and median 15 days after cycle 5 (follow-up). PET scans were read by a nuclear medicine physician, blinded to the results of clinical parameters. The most representative liver lesion was used as target lesion. PET results were quantified by calculating the maximum standard uptake value (SUVmax) at baseline and follow-up. PFS was defined as the time from start of treatment to the date of first documented disease progression. RESULTS Median PFS was 10 months (95% CI: 8.51-11.49). The median baseline SUVmax was 5.18 (IQR: 3.61-8.42) and the median follow-up SUVmax was 2.93 (IQR: 2.15-5.94; p=0.025). Following the EORTC criteria, FDG-PET revealed a complete metabolic response in 8 patients (44%), partial metabolic response in 3 patients (17%), stable metabolic disease in 3 patients (17%) and progressive metabolical disease in 4 patients (22%). Correlation between metabolic response and radiological response according to RECIST was as follows: 6 of the 8 patients with radiological response had metabolic response (sensitivity 75%) and 5 out of 10 patients with radiological stable or progressive disease were metabolic non-responders (specificity 50%). Using the Cox proportional hazards model, the follow-up SUVmax (HR 1.33, 95% CI 1.000-1.776, p=0.05) showed a trend towards significant prediction of PFS. The Kaplan-Meier log rank test showed a PFS benefit for patients with >30% reduction in their SUVmax (p=0.02). CONCLUSIONS The use of FDG-PET for therapy monitoring is clinically feasible and the follow-up SUVmax seems to be a promising predictor of PFS.

Preoperative chemotherapy for colorectal liver metastases : prediction of response by DCE-MRI abd FDG-PET/CT?

Human primary immunodeficiencies (PIDs) comprise a broad group of inherited disorders characterised by developmental or functional defects of myeloid or lymphoid haemapoietic-derived cells, as well as non-haemapoietic cells involved in protective immunity. More than 150 different forms of PIDs affecting distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, and T and B lymphocytes have been described [1]. Clinically, PIDs can be associated with any combination of infectious disease, autoimmunity, auto-inflammatory, allergy and malignancy. The best known PIDs show Mendelian inheritance and first become symptomatic during childhood. However, the field of PIDs is rapidly expanding and PIDs showing non-Mendelian inheritance and/or affecting primarily adult patients is being increasingly recognized. Conventional PIDs are typically seen as rare monogenic conditions associated with detectable immunologic abnormalities, resulting in a broad susceptibility to multiple and recurrent infections caused by weakly pathogenic and more virulent microorganisms. By opposition to these conventional PIDs, nonconventional primary immunodeficiencies as Mendelian conditions manifesting in otherwise healthy patients as a narrow susceptibility to infections, recurrent or otherwise, caused by weakly pathogenic or more virulent microbes are now reported [2]. By now, up to 120 diseasecausing genes have been identified. This molecular characterisation of PIDs has helped to increase our understanding of their physiopathology. The study of these diseases has provided essential insights into the functioning of the immune system with the ultimate goal of facilitating diagnosis and treatment.