Roland Bares

Fluorine-18 fluorodeoxyglucose positron emission tomography in the differential diagnosis of pancreatic carcinoma: a report of 106 cases

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) as a tool for the differential diagnosis of pancreatic carcinoma while taking into account serum glucose level. A group of 106 patients with unclear pancreatic masses were recruited for the study. PET was performed following intravenous administration of an average of 190 MBq [18F]FDG. Focally increased glucose utilisation was used as the criterion of malignancy. In addition, the \ldstandardised uptake value\rd (SUV) was determined 45 min after injection. Carcinoma of the pancreas was demonstrated histologically in 74 cases, and chronic pancreatitis in 32 cases. Employing visual evaluation, 63 of the 74 (85%) pancreatic carcinomas were identified by PET. In 27 of the 32 cases (84%) of chronic pancreatitis il was possible to exclude malignancy. False-negative results (n=11) were obtained mostly in patients with raised serum glucose levels (10 out of 11), and false-positives (n=5) in patients with inflammatory processes of the pancreas. Thus PET showed an overall sensitivity of 85%, a specificity of 84%, a negative predictive value of 71%, and a positive predictive value of 93%. In a subgroup of patients with normal serum glucose levels (n=72), the results were 98%, 84%, 96% and 93%, respectively. Quantitative assessment yielded a mean SUV of 6.4\+-3.6 for pancreatic carcinoma as against a value of 3.6\+-1.7 for chronic pancreatitis (P\s<0.001), without increasing the diagnostic accuracy. This shows PET to be of value in assessing unclear pancreatic masses. The diagnostic accuracy of PET examinations is very dependent on serum glucose levels.

Correlation of Stable Elevations in Striatal μ-Opioid Receptor Availability in Detoxified Alcoholic Patients With Alcohol Craving: A Positron Emission Tomography Study Using Carbon 11–Labeled Carfentanil

Main Outcome Measures: After 1 to 3 weeks of abstinence, the availability of μ-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in alcoholic patients compared with healthy controls and remained elevated when 12 alcoholic patients had these levels measured 5 weeks later (P .05 corrected for multiple testing). Higher availability of μ-opiate receptors in this brain area correlated significantly with the intensity of alcohol craving as assessed by the OCDS.

Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma

In the HD15 trial of the German Hodgkin Study Group, the negative predictive value (NPV) of positron emission tomography (PET) using [(18)F]-fluorodeoxyglucose in advanced-stage Hodgkin lymphoma (HL) was evaluated. A total of 817 patients were enrolled and randomly assigned to receive BEACOPP-based chemotherapy. After completion of chemotherapy, residual disease measuring more than or equal to 2.5 cm in diameter was assessed by PET in 311 patients. The NPV of PET was defined as the proportion of PET(-) patients without progression, relapse, or irradiation within 12 months after PET review panel. The progression-free survival was 96% for PET(-) patients (95% confidence interval [CI], 94%-99%) and 86% for PET(+) patients (95% CI, 78%-95%, P = .011). The NPV for PET in this analysis was 94% (95% CI, 91%-97%). Thus, consolidation radiotherapy can be omitted in PET(-) patients with residual disease without increasing the risk for progression or early relapse compared with patients in complete remission. The impact of this finding on the overall survival at 5 years must be awaited. Until then, response adapted therapy guided by PET for HL patients seems to be a promising approach that should be further evaluated in clinical trials. This trial is registered at http://isrctn.org study as #ISRCTN32443041.

PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study

The aim of this study was to evaluate the use of [18F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2–T4) were studied by FLT-PET. For comparison, [18F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUVmean=3.4±1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUVmean=2.4±1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUVFLT: 3.2 vs SUVFDG: 4.7 in primary tumours and SUVFLT: 2.9 vs SUVFDG: 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG (P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum.

18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

PurposeThe aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy (NARCT) of advanced non-small cell lung cancer (NSCLC).MethodsSeventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NARCT. Changes in FDG uptake and PET findings after completion of NARCT were compared with (1) the histology of tumour samples obtained at surgery or repeat mediastinoscopy, and (2) treatment results in terms of achieved operability and long-term survival.ResultsThe mean average FDG uptake of the primary tumours in the patient group decreased significantly during NARCT (p = 0.004). Sensitivity, specificity and overall accuracy of FDG-PET were 94.5%, 80% and 91%, respectively, for the detection of residual viable primary tumour, and 77%, 68% and 73%, respectively, for the presence of lymph node metastases. A negative PET scan or a reduction in the standardised uptake value (SUV) of more than 80% was the best predictive factor for a favourable outcome of further treatment. Progressive disease according to PET (new tumour manifestations or increasing SUV) was significantly correlated with an unfavourable outcome (p = 0.005). In this subgroup, survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery, whereas for the whole patient group, complete tumour resection had a significant influence on outcome.ConclusionFDG-PET is suitable to assess response to NARCT in patients with stage III NSCLC accurately. It was highly predictive for treatment outcome and patient survival. PET may be helpful in improving restaging after NARCT by allowing reliable assessment of residual tumour viability.

[18F]Fluorodeoxyglucose Positron Emission Tomography in Nonseminomatous Germ Cell Tumors After Chemotherapy: The German Multicenter Positron Emission Tomography Study Group

PURPOSE In patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospective trial has evaluated the accuracy of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the prediction of histology compared with computed tomography (CT) and serum tumor markers (STM). PATIENTS AND METHODS A total of 121 patients with stage IIC or III NSGCT scheduled for secondary resection after cisplatin-based CTX were included. FDG-PET was performed after completion of CTX. All results were confirmed by histopathology and correlated to STM and CT. RESULTS Prediction of tumor viability with FDG-PET was correct in 56%, which did not reach the expected clinically relevant level of 70%, and was not better than the accuracy of CT (55%) or STM (56%). Sensitivity and specificity of FDG-PET were 70% and 48%. The positive predictive values were not significantly different (55%, 61%, and 59% for CT, STM, and PET, respectively). Judging only vital carcinoma as a true malignant finding, the negative predictive value increased to 83% for FDG-PET. CONCLUSION The presence of vital carcinoma and mature teratoma is common (55%) in residual masses in patients with NSGCT, and CT and STM cannot reliably predict absence of disease. In contrast to prior studies, this prospective trial, which is the only with histologic confirmation in all patients, demonstrated that FDG-PET is unable to give a clear additional clinical benefit to the standard diagnostic procedures, CT and STM, in the prediction of tumor viability in residual masses.

Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype.

SummaryBackground. Homozygote carriers of two long (L) alleles of the serotonin transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an A > G exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [11C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of serotonin. Method. We assessed 5-HTT binding potential (BP2) in the midbrain of 19 healthy subjects with positron emission tomography and [11C]DASB. Accounting for the hypothesized functional similarity of LG and S in driving 5-HTT transcription, we assessed whether LALA homozygotes display increased midbrain BP2 compared with carriers of at least one S allele. Results. BP2 in the midbrain was significantly increased in LALA homozygotes compared with carriers of at least one S allele. Interestingly, the genotype effect on the midbrain was significantly different from that on the thalamus and the amygdala where no group differences were detected. Conclusions. This in vivo study provides further evidence that subjects homozygous for the LA allele display increased expression of 5-HTT in the midbrain, the origin of central serotonergic projections.

Histological verification of 11C-choline-positron emission/computed tomography-positive lymph nodes in patients with biochemical failure after treatment for localized prostate cancer.

To evaluate the potential of 11C‐choline‐positron emission tomography (PET)/computed tomography (CT) for planning surgery in patients with prostate cancer and prostate‐specific antigen (PSA) relapse after treatment with curative intent.

Is standardised 18F-FDG uptake value an outcome predictor in patients with stage III non-small cell lung cancer?

PurposeRecent studies have demonstrated the relevance of 18F-FDG uptake as an independent prognostic factor for recurrence of operable non-small cell lung cancer (NSCLC). This corresponds with the experimental finding that FDG uptake correlates with the proliferative activity of tumour cells (Higashi et al., J Nucl Med 2000;41:85-92). On the basis of these observations, we studied the influence of FDG uptake on prognosis and occurrence of distant metastases in patients with advanced NSCLC.MethodsOne hundred and fifty-nine patients with NSCLC of UICC stage IIIA or IIIB were included in the study. In all patients, neoadjuvant treatment was planned to achieve operability. FDG PET was performed as an additional staging procedure prior to the initiation of therapy. Clinical outcome data in terms of overall survival, disease-free survival and incidence of distant metastases could be obtained for 137 patients and were correlated with the average standardised uptake value of the tumour (SUVavg). Furthermore, other factors influencing SUVavg and patient outcome (histological tumour type, grading, UICC stage, tumour size) were analysed.ResultsSUVavg was significantly influenced by tumour histology, UICC stage and tumour size. No significant difference could be shown for grading. In 38 out of the 159 patients (24%), FDG PET revealed previously unsuspected distant metastases. The incidence of distant metastases significantly correlated with SUVavg. Overall survival tended to decrease with increasing SUVavg; however, significance was only reached when a cut-off of 12.0 was applied (p=0.05).ConclusionFDG uptake is an independent prognostic factor in patients with UICC stage III NSCLC, although less distinctively so than has been reported for stage I/II tumours.

Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study

Disseminated neuroblastoma after infancy has a prognosis of approximately 10-20% with conventional therapy. We investigated the role of high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) rescue in combination with 131I-metaiodobenzylguanidine ([131I-m]IBG). 11 children with neuroblastoma stage 4 were pretreated within the German Neuroblastoma Trial NB90 and included in a high-dose concept for consolidation. Remission was documented by ultrasound, CT, NMR, or [123I-m]IBG scanning. HDCT was a combination of melphalan (180 mg/m2), carboplatin (1,500 mg/m2) and etoposide (40 mg/kg). All children were treated by [131I-m]IBG (0.58 GBq/kg) prior to high-dose treatment. All 11 children were additionally treated with antiGD2 murine- or chimeric-antibody (ch14.18). 4 children had no change to their remission status but three achieved a complete response (from a partial response to first line) and one a partial response (from no response to first line). The other 3 children progressed, 2 dying of their disease. Using Kaplan-Meier analysis, the probability of progression-free survival was 0.70 +/- 0.15 with a median observation time of 19 months. 9/11 children are alive, 8 without progression or relapse, whilst 2 have died of their disease. The combination of mIBG plus high-dose chemotherapy with PBSC support supplemented by immunotherapy with antiGD2 antibody appears to be a feasible and effective treatment regimen for disseminated neuroblastoma in this limited series. Larger numbers of patients should be treated to confirm these results.