[Staging with 18F-FDG-PET/CT influences stage-specific survival in advanced non-small cell lung cancer (NSCLC)]. / Der Einfluss des F-18-FDG-PET/CT auf das stadienbezogene Gesamtüberleben beim fortgeschrittenen nicht-kleinzelligen Lungenkarzinom (NSCLC).

BACKGROUND: PET/CT investigation with 18F-fluorodeoxyglucose (FDG) has a high sensitivity (89 - 100 %) and good specificity (79 - 95 %) for the diagnosis of NSCLC. Currently, it is mainly used in preoperative staging. This leads in approximately 15 % of these cases to the diagnosis of metastatic disease that was neither clinically suspected nor seen in previously performed conventional imaging. We hypothesised that including these cases in the palliative stage IV group would have an influence on overall survival. AIM: The aim of this study was to compare the overall survival (OS) of patients with stage IV NSCLC who underwent FDG-PET/CT staging with patients in whom conventional imaging procedures were performed. METHODS: We analysed the OS of all stage IV NSCLC patients diagnosed in our clinic in 2009 (n = 254), 96/254 (38 %) patients were staged with PET/CT and 158/254 (62 %) with conventional imaging (CT group). Survival data were compared by Kaplan-Meier statistics. RESULTS: Patients in the PET/CT group were younger (65 ± 11) than in the CT group (68 ± 10 years; p = 0.008). The median OS of all patients was 246 (range: 217 - 275) days; 338 (range: 247 - 429) days in the PET/CT group and 207 (range: 161 - 253) days in the CT group (p = 0.001), stating a difference of 131 days (4.4 months) in median OS. CONCLUSION: The use of FDG-PET/CT staging mainly in the preoperative setting leads to stage migration of patients with a better prognosis into the worst stage (IV) and thus longer survival within this subgroup. This survival benefit is unrelated to treatment and needs to be addressed in future studies.

Somatostatin receptor scintigraphy in thyroid eye disease.

Orbital lymphocytic infiltration in thyroid eye disease (TED), as well as identification of somatostatin (SMS) receptors on activated lymphocytes, has provided a rationale for receptor imaging with the radiolabeled SMS analog Pentetreotide. In 80 patients with TED, single-photon emission computed tomography (SPECT) images of the orbit were performed 4 and 24 hours after injection of Pentetreotide. Semiquantitative evaluation was performed using the SPECT slices with irregular regions of interests placed over the orbits and both hemispheres. In contrast to controls (median 5 counts per voxel per millibecquerel (cts/vox/MBq) injected activity), TED patients showed threefold increased orbital accumulation of Pentetreotide (15 cts/vox/MBq, p = 0.003). When considering patients with active TED only, even higher uptake was registered (23 cts/vox/MBq, p = 0.0006 vs. controls, sensitivity for active TED 61/68, 90%; specificity 12/12, 100%). In 40 patients with active TED, the radionuclide accumulation decreased sharply after completion of immunosuppressive therapy. A high pretreatment Pentetreotide orbit-to-brain ratio correlated with a response to therapy (positive and negative predictive values 28/32, 88%, and 8/8, 100%, respectively). In conclusion, SMS receptor scintigraphy may be regarded as a semiobjective tool in the evaluation of TED, both at initial stages as well as during treatment.

Somatostatin-receptor scintigraphy in Graves' disease: reproducibility and variance of orbital activity.

Somatostatin-receptor (SSTR) scintigraphy using the single photon emission computed tomography (SPECT) technique allows the assessment of orbital inflammation in patients with Graves' disease. Previous studies showed differences in orbital octreotide uptake already 4 hr after injection. In this study, analysis of inter-/intra-observer variance and reproducibility in the evaluation of orbital SPECT images was performed. First, SPECT data of one representative female patient with clinically active Graves' ophthalmopathy (GO), obtained 4 hr after intravenous injection of 110 MBq 111In-pentetreotide and processed by filtered backprojection, were analyzed. Transverse SPECT images were reconstructed, an optimal orbital image was selected and predetermined regions of interests (ROIs) for both orbits were positioned by three independent observers 15 to 19 times each. In a second step, SPECT data of 8 different patients with GO were evaluated in the same manner by four independent observers 3 to 4 times each. Variance component partitioning was used to compare the order of intra- and inter-observer variation. For the right and the left orbit, the inter-observer variance proportion was 90% and 79%, whereas intra-observer variance partition was 10% and 21%, respectively. The corresponding ratios 0.11 and 0.27 summarize the comparison of sources of variance. The overall reliability was 84%, representing the patients influence on the total variance. Intra-observer reliability for both orbits was 88%, 89%, 97% and 98% (mean over orbits), respectively for observers I to IV. Using the Spearman Brown prophecy formula it follows that two replications per patient are sufficient to ensure a minimum reproducibility of 90%, which is also confirmed by the low intra-observer variation. Furthermore, intra-class correlation as a measure of (multiple) observer reproducibility was 94%. In conclusion, due to the increased inter-observer variance proportion and the high variation in intra-observer reliability, evaluations of orbital SSTR scintigraphy have to be done by the same and experienced observer leading to comparable data. But an automatic and quantitative computerized technique for evaluation of these SPECT data should be exactly reproducible and probably lead to more accurate and representative results.

[(18F)-2-fluorodeoxyglucose PET. Prospects for secondary prevention of mouth cavity carcinoma]. / [18F]-2-Fluordeoxyglukose-PET. Perspektiven der Sekundärprophylaxe des Mundhöhlenkarzinoms.

AIMS: The predominant cause of death due to oral cancer is the failure to control local tumor due to regional tumor recurrence. The sequelae of surgical resection and high-dose irradiation cause substantial changes in head and neck anatomy, leading to considerable problems in the early morphological detection of recurrent disease. Therefore, this study evaluates the verification of cancer recurrence by means of its pathologic glucose metabolism. MATERIALS AND METHODS: We reviewed a total of 50 [18F]-2-fluordeoxyglucose positron emission tomography (18FDG-PET) investigations performed in 44 patients who had undergone surgical resection of oral cancer. In 23 cases, re-staging (group A) was indicated due to suspicion of recurrent or secondary tumor manifestation. In 27 cases, PET served as a screening procedure (group B). Statistic evaluation included sensitivity, specificity, positive/negative predictive value and accuracy of 18FDG-PET for the detection of tumor manifestation. RESULTS: 18FDG-PET correctly identified 23 of 26 tumor sites (88%) in the re-staging group and 9 of 10 tumor sites (90%) in the screening group. We encountered a total number of 16 false-positive foci with an increased 18FDG-uptake. In six patients, 18FDG-PET detected tumor recurrence several months before a morphological correlative could be identified. In 5 of these 6 patients, the PET findings for the latter tumor sites determined the patient's fate. Specificity was 63% for local recurrence, 97% for secondary lymph node involvement and 90% for distant metastasis. CONCLUSION: According to these data, 18FDG-PET is the most effective diagnostic tool in the follow-up of oral cancer patients to date. Due to the high prevalence of recurrent disease in the follow-up of oral cancer, either the detection of early recurrence or the identification of additional, incurable tumors may add substantially to a rational therapeutic management. We therefore recommend 18FDG-PET for screening and re-staging of recurrent oral cancer.

[Therapy monitoring with 2-(18F)-FDG positron emission tomography after neoadjuvant radiation treatment of mouth carcinoma]. / Therapiemonitoring mittels 2-[18F]-FDG-Positronenemissionstomographie nach neoadjuvanter Strahlenbehandlung des Mundhöhlenkarzinoms.

BACKGROUND: Combined protocols of radiation therapy and surgical resection, as applied in advanced oral cancer, rely on objective and early assessment of treatment response to radiation therapy. Non-responders require immediate radical salvage surgery even in spite of substantial operative risks, while complete or subtotal response may give reasons for continuing the conservative approach. Therefore, we investigated radiation response by FDG-PET for early monitoring of oral cancer. PATIENTS AND METHODS: In 30 patients with advanced stages of oral cancer (Table 1), FDG-PET (Siemens, ECAT EXACT 922) was performed within 4 weeks after completion of preoperative radiation therapy (36 Gy). SUV of tumor regions were compared to the histologic degree of tumor regression in complete resection specimens. Statistic evaluation included correlation analysis of SUV vs tumor regression and ROC analysis for SUV cut-off values. RESULTS: While low FDG accumulation was found in tumors with histological complete remission (2.3 +/- 0.4) as well as in cases of residual tumor (3.4 +/- 1.8), high FDG uptake was a rather specific indicator of vital tumor tissue (Figure 2). Significant correlation (p = 0.045) between postradiotherapeutic FDG-uptake and histological tumor regression was recognized. A SUV > 2.75 as a clinically practicable threshold value for the identification of residual vital tumor resulted in a specificity of 88%, sensitivity of 68%, a positive predictive value of 94% and a negative predictive value of 50% (Figure 3). Based on our actual follow-up data we could not confirm a significant correlation between postradiotherapeutic SUV and patients' survival. CONCLUSION: Within a standardized protocol, FDG-PET recognize treatment response to radiation therapy in oral squamous cell carcinoma with a reasonable specificity and thus provides a basis for further therapeutic decisions. An increased SUV (> 2.75) may be the rational to justify an aggressive surgical approach even when patients face substantial surgical or anesthesiological risk. However, the posttherapeutic pattern of glucose uptake varies with the applied treatment modalities and has to be explored for the protocol applied.

PET imaging with yttrium-86: comparison of phantom measurements acquired with different PET scanners before and after applying background subtraction.

Quantitative imaging with the positron emitter (86)Y is the method of choice to determine the uptake and dosimetry of (90)Y-labelled radiopharmaceuticals. To examine the quantitative accuracy of positron emission tomography findings with (86)Y, this non-pure positron emitter was evaluated in a cylindrical phantom with rods of Teflon, water and air and measured with three different scanners: ECAT EXACT (2D/3D), ECAT HR+ (2D/3D) and PC4096+ (2D). After standard reconstruction, (86)Y radioactivity measured with the ECAT EXACT and related to the true radioactivity varied between 0.84 and 0.99 in 2D and between 0.93 and 1.20 in 3D from the first to the last acquisition (eight half-life times later). The water and Teflon rods exhibited considerable amounts of reconstructed radioactivity-21% in 2D and 67% in 3D for water and 65% and 147%, respectively, for Teflon-compared with the actual (86)Y radioactivity of the phantom. For the ECAT HR+ similar results were obtained in 3D, but there were even greater overestimations in 2D. Measurements with the PC4096+ showed rather small errors, with 10% for water and 20% for Teflon. To correct for the background of gamma-coincidences, sinograms were analysed and an experimental percentage of the background was subtracted from the sinograms. In order to minimise the errors in reconstructed radioactivity, the subtraction value had to be different for the individual scanners and modes. Our results demonstrate that (90)Y/(86)Y-based dosimetry for bone and red marrow must be regarded with caution if it is derived from regions of interest over the bone, the density of which is similar to that of Teflon. To obtain more reliable estimates, an appropriate background correction must be applied and tailored individually with respect to the scanner and acquisition mode.

Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of (86)Y-DOTATOC and (111)In-DTPA-octreotide.

The somatostatin analogue (90)Y-DOTATOC (yttrium-90 DOTA- D-Phe(1)-Tyr(3)-octreotide) is used for treatment of patients with neuroendocrine tumours. Accurate pretherapeutic dosimetry would allow for individual planning of the optimal therapeutic strategy. In this study, the biodistribution and resulting dosimetric calculation for therapeutic exposure of critical organs and tumour masses based on the positron emission tomography (PET) tracer (86)Y-DOTATOC, which is chemically identical to the therapeutic agent, were compared with results based on the tracer commonly used for somatostatin receptor scintigraphy, (111)In-DTPA-octreotide (indium-111 DTPA- D-Phe(1)-octreotide, OctreoScan). Three patients with metastatic carcinoid tumours were investigated. Dynamic and static PET studies with 77-186 MBq (86)Y-DOTATOC were performed up to 48 h after injection. Serum and urinary activity were measured simultaneously. Within 1 week, but not sooner than 5 days, patients were re-investigated by conventional scintigraphy with (111)In-DTPA-octreotide (110-187 MBq) using an equivalent protocol. Based on the regional tissue uptake kinetics, residence times were calculated and doses for potential therapy with (90)Y-DOTATOC were estimated. Serum kinetics and urinary excretion of both tracers showed no relevant differences. Estimated liver doses were similar for both tracers. Dose estimation for organs with the highest level of radiation exposure, the kidneys and spleen, showed differences of 10.5%-20.1% depending on the tracer. The largest discrepancies in dose estimation, ranging from 23.1% to 85.9%, were found in tumour masses. Furthermore, there was a wide inter-subject variability in the organ kinetics. Residence times (tau(organs)) for (90)Y-DOTATOC therapy were: tau(liver) 1.59-2.79 h; tau(spleen) 0.07-1.68 h; and tau(kidneys) 0.55-2.46 h (based on (86)Y-DOTATOC). These data suggest that dosimetry based on (86)Y-DOTATOC and (111)In-DTPA-octreotide yields similar organ doses, whereas there are relevant differences in estimated tumour doses. Individual pretherapeutic dosimetry for (90)Y-DOTATOC therapy appears necessary considering the large differences in organ doses between individual patients. If possible, the dosimetry should be performed with the chemically identical tracer (86)Y-DOTATOC.