Bernd J. Krause

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information.

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

Preliminary results for characterization of pelvic lymph nodes in patients with prostate cancer by diffusion-weighted MR-imaging.

Objectives:In this retrospective feasibility study diffusion-weighted magnetic resonance imaging (DWI) was evaluated as a potential tool for characterization of pelvic lymph nodes in patients with prostate cancer. Methods and Materials:Twenty-nine patients with prostate cancer underwent DWI of the pelvis at 1.5T by a non breath-hold SSEPI sequence using a body phased array coil with b values of 50, 300, and 600 s/mm2 and an additional T2-weighted sequence. A total of 118 lymph nodes (>6 mm short axis) were analyzed by measuring the ADC-value with a polygon region of interest. Feasibility for ADC-measurement was assessed by comparing the ADC-value from the automatically created ADC-map (ADCMR_unit) with a manually calculated ACD-value (ADCcalculated) and by using a linear-regression model for comparison with size and standard deviation of the ADC-value. Diagnostic performance was estimated by receiver operator characteristic analysis using histologic and/or clinical follow-up as standard of reference. Results:ADCMR_unit and ADCcalculated showed a high correlation (r = 0.8999) with a mean percentual deviation of 6.33%. There was a highly significant difference between the mean ADC-value (×10−3 mm2/s) of malignant (1.07 ± 0.23) versus benign (1.54 ± 0.25) lymph nodes, even in subgroup analysis for lymph nodes smaller versus larger than 10 mm. Receiver operator characteristic-analysis showed a good accuracy of the ADC-value (85.6% [101/118]; sensitivity: 86.0% [43/50]; specificity: 85.3% [53/68]) for differentiation of malignant and benign lymph nodes at a cutoff 1.30 × 10−3 mm2/s. This was superior to a size-based analysis at a cutoff of 8 mm (accuracy: 66.1% [78/118]; sensitivity: 82.0% [41/50]; specificity: 54.4% [37/68]; P < 0.01). Conclusions:DWI has the potential of being an accurate technique for analysis of pelvic lymph nodes. Moreover, our preliminary results suggest that the ADC-value might perform significantly superior to size criteria to discriminate between benign and malignant lymph nodes.

Economic Evaluation of PET and PET/CT in Oncology: Evidence and Methodologic Approaches

PET and PET/CT have changed the diagnostic algorithm in oncology. Health care systems worldwide have recently approved reimbursement for PET and PET/CT for staging of non–small cell lung cancer and differential diagnosis of solitary pulmonary nodules because PET and PET/CT have been found to be cost-effective for those uses. Additional indications that are covered by health care systems in the United States and several European countries include staging of gastrointestinal tract cancers, breast cancer, malignant lymphoma, melanoma, and head and neck cancers. Regarding these indications, diagnostic effectiveness and superiority over conventional imaging modalities have been shown, whereas cost-effectiveness has been demonstrated only in part. This article reports on the current knowledge of economic evaluations of PET and PET/CT in oncologic applications. Because more economic evaluations are needed for several clinical indications, we also report on the methodologies for conducting economic evaluations of diagnostic tests and suggest an approach toward the implementation of these tests in future clinical studies.

Early Metabolic Response Evaluation by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Allows In vivo Testing of Chemosensitivity in Gastric Cancer: Long-term Results of a Prospective Study

Purpose: We prospectively evaluated the predictive value of positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) for in vivo testing of chemosensitivity in locally advanced gastric cancer using an a priori definition of metabolic response (a decrease of >35% of the standard uptake value). The goal of the study was the definition of biologically different groups of patients prior to or early during induction therapy, with special emphasis on FDG non–avid tumors. Experimental Design: Based on our data, which was published in 2003, at least 36 patients with metabolic response or FDG non–avid tumors had to be recruited for an analysis of the group of FDG non–avid tumors with sufficient statistical power. Seventy-one patients (32 metabolic nonresponders, 17 metabolic responders, and 22 patients with FDG non–avid tumors) underwent FDG-PET at baseline. In FDG-avid tumors, FDG-PET was repeated 14 days after the initiation of chemotherapy. Results: Metabolic responders (17 of 49) showed a high histopathologic response rate (69%) and a favorable prognosis (median survival not reached), whereas metabolic nonresponders (32 of 49) had a poor prognosis (median survival, 24.1 months) and showed a histopathologic response in 17%. The histopathologic response rate (24%) for FDG-PET non–avid patients showed no significant difference compared with FDG-avid nonresponders (P = 0.72). Survival of FDG non–avid patients was 36.7 months (not significantly different from FDG-avid nonresponders, 24.1 months, P = 0.46). Conclusion: In locally advanced gastric cancer, three different metabolic groups exist. Response and survival was predicted by PET in FDG-avid tumors. Metabolic response assessment was not possible in FDG non–avid tumors; however, due to unfavorable outcome, therapy modification might also be considered in FDG non–avid tumors.

(18)F-FDG PET-guided salvage neoadjuvant radiochemotherapy of adenocarcinoma of the esophagogastric junction : the MUNICON II trial

Previous studies demonstrated that chemotherapy-induced changes in tumor glucose metabolism measured with 18F-FDG PET identify patients who benefit from preoperative chemotherapy and those who do not. The prognosis for chemotherapy metabolic nonresponders is poorer than for metabolic responders. Therefore, we initiated this prospective trial to improve the clinical outcome of metabolic nonresponders using a salvage neoadjuvant radiochemotherapy. Methods: Fifty-six patients with locally advanced adenocarcinomas of the esophagogastric junction were included. Tumor glucose uptake was assessed by 18F-FDG PET before chemotherapy and 14 d after initiation of chemotherapy. PET nonresponders received salvage neoadjuvant radiochemotherapy, whereas metabolic responders received neoadjuvant chemotherapy for 3 mo before surgery. Results: Thirty-three patients were metabolic responders, and 23 were nonresponders. Resection was performed on 54 patients. R0 resection rate was 82% (95% confidence interval [CI], 66%–91%) in metabolic responders and 70% (95% CI, 49%–84%) in metabolic nonresponders (P = 0.51). Major histologic remissions were observed in 12 metabolic responders (36%; 95% CI, 22%–53%) and 6 nonresponders (26%; 95% CI, 13%–46%). One-year progression-free rate was 74% ± 8% in PET responders and 57% ± 10% in metabolic nonresponders (log rank test, P = 0.035). One-year overall survival was comparable between the groups (∼80%), and 2-y overall survival was estimated to be 71% ± 8% in metabolic responders and 42% ± 11% in PET nonresponders (hazard ratio, 1.9; 95% CI, 0.87–4.24; P = 0.10). Conclusion: This prospective study showed the feasibility of a PET-guided treatment algorithm. However, by comparing the groups of nonresponding patients in the current trial and the previous published MUNICON (Metabolic response evalUatioN for Individualisation of neoadjuvant Chemotherapy in Esophageal and esophagogastric adeNocarcinoma) I trial, increased histopathologic response was observed after salvage radiochemotherapy, but the primary endpoint of the study to increase the R0 resection rate was not met. The prognosis of the subgroup of PET nonresponders remains poor, indicating their different tumor biology.

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

177Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients. Methods: One hundred forty-five patients (median age, 73 y; range, 43–88 y) with mCRPC were treated with 177Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1–4 therapy cycles and an activity range of 2–8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician’s report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline ≥ 50% from baseline to at least 2 wk after the start of RLT. Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2–30 wk). Nineteen patients died during the observation period. Grade 3–4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. Conclusion: The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.

Clinical Applications of FDG PET and PET/CT in Head and Neck Cancer

18F-FDG PET plays an increasing role in diagnosis and management planning of head and neck cancer. Hybrid PET/CT has promoted the field of molecular imaging in head and neck cancer. This modality is particular relevant in the head and neck region, given the complex anatomy and variable physiologic FDG uptake patterns. The vast majority of 18F-FDG PET and PET/CT applications in head and neck cancer related to head and neck squamous cell carcinoma. Clinical applications of 18F-FDG PET and PET/CT in head and neck cancer include diagnosis of distant metastases, identification of synchronous 2nd primaries, detection of carcinoma of unknown primary and detection of residual or recurrent disease. Emerging applications are precise delineation of the tumor volume for radiation treatment planning, monitoring treatment, and providing prognostic information. The clinical role of 18F-FDG PET/CT in N0 disease is limited which is in line with findings of other imaging modalities. MRI is usually used for T staging with an intense discussion concerning the preferable imaging modality for regional lymph node staging as PET/CT, MRI, and multi-slice spiral CT are all improving rapidly. Is this review, we summarize recent literature on 18F-FDG PET and PET/CT imaging of head and neck cancer.

Imaging Gastric Cancer with PET and the Radiotracers 18F-FLT and 18F-FDG: A Comparative Analysis

In this pilot study, we evaluated 3′-deoxy-3′-18F-fluorothymidine (FLT) PET for the detection of gastric cancer and compared the diagnostic accuracy with that of 18F-FDG PET. Methods: Forty-five patients (31 male and 14 female) with histologically proven locally advanced gastric cancer underwent attenuation-corrected whole-body 18F-FLT PET and 18F-FDG PET/CT (low-dose CT). 18F-FLT emission images were acquired on a full-ring PET scanner 45 min after the injection of 270–340 MBq of 18F-FLT. 18F-FDG PET/CT was performed 60 min after the injection of 300–370 MBq of 18F-FDG. Mean standardized uptake values for 18F-FLT and 18F-FDG were calculated using circular ROIs (diameter, 1.5 cm) in the primary tumor manifestation site, in a reference segment of the liver, and in the bone marrow and were compared on a lesion-by-lesion basis. Results: According to the Lauren classification, 15 tumors (33%) were of the intestinal subtype and 30 (67%) of the nonintestinal subtype. 18F-FLT PET images showed high contrast for the primary tumor and proliferating bone marrow. In all patients (45/45), focal 18F-FLT uptake could be detected in the primary tumor. In contrast, 14 primary tumors were negative for 18F-FDG uptake, with lesional 18F-FDG uptake lower than or similar to background activity. The mean standardized uptake value for 18F-FLT in malignant primaries was 6.0 ± 2.5 (range, 2.4–12.7). In the subgroup of 18F-FDG–positive patients, the mean value for 18F-FDG was 8.4 ± 4.1 (range, 3.8/19.0), versus 6.8 ± 2.6 for 18F-FLT (Wilcoxon test: P = 0.03). Comparison of mean 18F-FLT and 18F-FDG uptake in tumors with signet ring cells revealed no statistically significant difference between the tracers (6.2 ± 2.1 for 18F-FLT vs. 6.4 ± 2.8 for 18F-FDG; Wilcoxon test: P = 0.94). Conclusion: The results of this study indicate that imaging gastric cancer with the proliferation marker 18F-FLT is feasible. 18F-FLT PET was more sensitive than 18F-FDG PET, especially in tumors frequently presenting without or with low 18F-FDG uptake, and may improve early evaluation of response to neoadjuvant treatment.

The sensitivity of [11C]choline PET/CT to localize prostate cancer depends on the tumor configuration.

Purpose: To evaluate the dependency of the sensitivity of [11C]choline positron emission tomography/computed tomography (PET/CT) for detecting and localizing primary prostate cancer (PCa) on tumor configuration in the histologic specimen. Experimental Design: Forty-three patients with biopsy-proven PCa were included. They underwent radical prostatectomy within 31 days after [11C]choline PET/CT. The transaxial image slices and the histologic specimens were analyzed by comparing the respective slices. Maximum standardized uptake values (SUVmax) were calculated in each segment and correlated with histopathology. The tumor configuration in the histologic specimen was grouped as: I, unifocal; II, multifocal; III, rind-like shaped; IV, size <5 mm. Data analysis included the investigation of detection of PCa by SUVmax, the assessment of the influence of potential contributing factors on tumor prediction, and the evaluation of whether SUV could discriminate cancer tissue from benign prostate hyperplasia (BPH), prostatitis, HGPIN (high-grade prostate intraepithelial neoplasm), or normal prostate tissue. General estimation equation models were used for statistical analysis. Results: Tumor configuration in histology was classified as I in 21 patients, as II in 9, as III in 5, and as IV in 8. The prostate segment involved by cancer is identified in 79% of the patients. SUVmax was located in the same side of the prostate in 95% of patients. Tumor configuration was the only factor significantly negatively influencing tumor prediction (P < 0.001). PCa-SUVmax (median SUVmax = 4.9) was not significantly different from BPH-SUV (median SUVmax = 4.5) and prostatitis-SUV (median SUVmax = 3.9), P = 0.102 and P = 0.054, respectively. Conclusions: The detection and localization of PCa in the prostate with [11C]choline PET/CT is impaired by tumor configuration. Additionally, in our patient population, PCa tissue could not be distinguished from benign pathologies in the prostate. Clin Cancer Res; 17(11); 3751–9. ©2011 AACR.