Machine learning predictive performance evaluation of conventional and fuzzy radiomics in clinical cancer imaging cohorts.

BACKGROUND: Hybrid imaging became an instrumental part of medical imaging, particularly cancer imaging processes in clinical routine. To date, several radiomic and machine learning studies investigated the feasibility of in vivo tumor characterization with variable outcomes. This study aims to investigate the effect of recently proposed fuzzy radiomics and compare its predictive performance to conventional radiomics in cancer imaging cohorts. In addition, lesion vs. lesion+surrounding fuzzy and conventional radiomic analysis was conducted. METHODS: Previously published 11C Methionine (MET) positron emission tomography (PET) glioma, 18F-FDG PET/computed tomography (CT) lung, and 68GA-PSMA-11 PET/magneto-resonance imaging (MRI) prostate cancer retrospective cohorts were included in the analysis to predict their respective clinical endpoints. Four delineation methods including manually defined reference binary (Ref-B), its smoothed, fuzzified version (Ref-F), as well as extended binary (Ext-B) and its fuzzified version (Ext-F) were incorporated to extract imaging biomarker standardization initiative (IBSI)-conform radiomic features from each cohort. Machine learning for the four delineation approaches was performed utilizing a Monte Carlo cross-validation scheme to estimate the predictive performance of the four delineation methods. RESULTS: Reference fuzzy (Ref-F) delineation outperformed its binary delineation (Ref-B) counterpart in all cohorts within a volume range of 938-354987 mm3 with relative cross-validation area under the receiver operator characteristics curve (AUC) of +4.7-10.4. Compared to Ref-B, the highest AUC performance difference was observed by the Ref-F delineation in the glioma cohort (Ref-F: 0.74 vs. Ref-B: 0.70) and in the prostate cohort by Ref-F and Ext-F (Ref-F: 0.84, Ext-F: 0.86 vs. Ref-B: 0.80). In addition, fuzzy radiomics decreased feature redundancy by approx. 20%. CONCLUSIONS: Fuzzy radiomics has the potential to increase predictive performance particularly in small lesion sizes compared to conventional binary radiomics in PET. We hypothesize that this effect is due to the ability of fuzzy radiomics to model partial volume effects and delineation uncertainties at small lesion boundaries. In addition, we consider that the lower redundancy of fuzzy radiomic features supports the identification of imaging biomarkers in future studies. Future studies shall consider systematically analyzing lesions and their surroundings with fuzzy and binary radiomics.

Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI.

PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

Sex-differences in [68Ga]Ga-DOTANOC biodistribution.

INTRODUCTION: Still little is known about factors, influencing the organ uptake of somatostatin receptor (SSTR)-targeting radiopharmaceuticals. The aim of this study was to assess the influence of gender on [68Ga]Ga-DOTANOC uptake. Further on, we assessed other factors such as diabetes, proton pump inhibitors (PPIs) and oral antidiabetics (OADs). METHODS: In 118 studies of patients with a [68Ga]Ga-DOTANOC PET/CT (m = 60, f = 58; mean age: 61 ±â€¯15 yrs) SUVmax and SUVmean of the stomach, liver, spleen, kidneys, adrenal glands, and pancreas were assessed. Patients with history of splenectomy and significant tumor burden were excluded. Additionally, clinical information (gender, diabetes, age, pre-medications such as PPIs, OADs and somatostatin analogues (SSAs), were collected. RESULTS: [68Ga]Ga-DOTANOC uptake proved to be significantly lower in female patients compared to males for the SUVmax of the stomach (7.1, 9.1; P = 0.04), liver (8.3, 9.4; P = 0.0007), adrenal glands (15.9, 19.9; P = 0.05) kidneys (20.3, 18.9; P = 0.05) and the SUVmean of the pancreatic tail (2.9, 3.2; P = 0.03) and the kidneys (11.8, 10.6, P = 0.004). Additionally, patients with diabetes and below the age of 50 yrs. showed significantly higher SUVmax and SUVmean values of the stomach (diabetes: 9.1, 7.8; P = 0.01 and 6.0, 5.3; P = 0.004; age: 6.3, 8.3; P = 0.01 and 4.4, 5.5; P = 0.03). In contrast, intake of PPIs only affected the SUVmean of the liver (11.0, 9.0; P = 0.005), whereas OADs caused higher SUVmax values in the stomach (10.0, 7.8; P = 0.02), spleen (42.5, 32.6; P = 0.0005) adrenal glands (25.0, 16.9; P = 0.0003) and also higher SUVmean in the spleen (26.1, 21.4; P = 0.002) and adrenal glands (14.8, 12.4; P = 0.02). CONCLUSION: Factors such as gender, diabetes and age influence [68Ga]Ga-DOTANOC uptake, whereas ongoing medications such as PPIs and OADs exerted less influence.

68Ga-PSMA 11 ligand PET imaging in patients with biochemical recurrence after radical prostatectomy - diagnostic performance and impact on therapeutic decision-making.

OBJECTIVE: To evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions. MATERIAL AND METHODS: We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making. RESULTS: The median time from RP to BCR was 36 months (IQR 16-72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58-1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. CONCLUSIONS: We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.

Hematopoiesis is prognostic for toxicity and survival of 223Radium treatment in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: We evaluated the impact of pre-therapeutic hematopoiesis on survival, hematotoxicity (HT) and number of 223Radium (223Ra) treatments in patients with metastatic castration-resistant prostate cancer. SUBJECTS AND METHOD: Hemoglobin-levels (Hb), the number of platelets (Plts), leukocytes (Leuk), and survival data were collected in 56 patients treated with 223Ra. Pre-therapeutic hematopoiesis as well as adverse events during and after therapy were scored (grade 0-4) according to the CTCAE recommendations. The association of pre-therapeutic hematopoiesis, survival, HT and numbers of 223Ra cycles was analyzed. RESULTS: Median survival in all patients was 69.9 weeks; 77% of patients had pre-existing impaired Hb (1.7% grade 3, 12.5% grade 2, 62.5% grade 1). 8/56 (14.3%) had impaired Plt (grade 1) Maximum toxicity (Tox) grades of patients during treatment were grade 4 (Hb 1.7%; Plt 1.7%), grade 3 (Hb 14.3%; Plt 7.1%; Leu 7.1%), grade 2 (Hb 33.9%; Plt 7.1%; Leu 23.2%), grade 1 (Hb 46.4%; Plt 17.9%; Leu 23.2%) and grade 0 (Hb 5.4%; Plt 66.1%; Leu 44.6%). Interestingly, patients with thrombocytopenia had a significantly shorter survival compared to those with normal Plt levels (21 weeks vs not reached; P<0.003). As expected patients with pre-therapeutic low Hb-level (<10g/dL) had a significantly shorter survival compared to those with Hb-level >10g/dL (28 weeks vs not reached, P<0.004), whereas survival of patients with mildly impaired Hb (>10 but <13.5g/dL) did not differ from patients with normal levels of Hb (X vs. Y, P=...). Also patients with impaired Hb also developed significantly more grade 3 and 4 HT (Hb <10g/dL: 42.9 vs 14.3%, P<0.001; Plt <150G/mL: 25.0% vs 6.3%; P=0.002) and received significantly fewer treatment cycles (Hb<10g/dL: 5.1 vs 5.8, P<0.04; Plt <150G/mL: 3.4 vs 5.6; P<0.001). Neither extent of bone metastases nor previous chemotherapy were associated with survival, number of 223Ra cycles and HT. CONCLUSION: Patients with metastatic castration-resistant prostate cancer and impaired hematopoiesis, in particular thrombocytopenia and anemia, before 223Ra therapy suffer from significantly more high-grade HT, shorter survival and receive significantly fewer 223Ra treatments. Therefore, Hb-levels and platelet counts are essential parameters for adequate patient selection for 223Ra therapy.

Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma.

Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.

[Hemato-oncological imaging : Importance of hybrid procedures]. / Hämatoonkologische Bildgebung : Stellenwert der Hybridverfahren.

CLINICAL/METHODICAL ISSUE: Biomedical imaging procedures play a major role in hemato-oncological diseases with respect to pre-therapeutic staging and assessment of treatment response. STANDARD RADIOLOGICAL METHODS: Originally, the therapeutic management was the domain of computed tomography (CT) and whole-body magnetic resonance imaging (MRI). METHODICAL INNOVATIONS: Over the last decade these purely morphological techniques have gradually been replaced by hybrid imaging techniques, such as positron emission tomography-CT (PET/CT) and PET/MRI, which also provide metabolic and functional information. PERFORMANCE: For lymphomas, the PET tracer 18F-fluorodeoxyglucose (18 F-FDG) is meanwhile so well-established that its use is a cornerstone of the Lugano classification; however, for multiple myeloma the search for an optimal PET tracer that can also detect early disease stages is still ongoing. Functional MRI techniques, such as diffusion-weighted imaging (DWI), perfusion-weighted imaging and dynamic contrast-enhanced imaging have shown promising results for both lymphomas and multiple myelomas. ACHIEVEMENTS: The PET/MRI technique can combine the different types of information due to its truly multiparametric approach. PRACTICAL RECOMMENDATIONS: In the future PET/MRI could possibly become the hybrid imaging technique of choice for hemato-oncological diseases.

Approximation of head and neck cancer volumes in contrast enhanced CT.

BACKGROUND: Tumor volume may serve as a predictor of response to radiochemotherapy (RCT) in head and neck squamous cell carcinoma (HNSCC). Computer assisted tumor volumetry requires time-consuming slice-by-slice manual or semi-automated segmentation. We questioned how accurately primary tumor and suspect cervical lymph node (LN) volumes can be approximated by the maximum tumor diameters in three dimensions. METHODS: In contrast-enhanced diagnostic CT scans of 74 patients with incident advanced HNSCC, manual slice-by-slice segmentation volumetry of primary tumor, total- and largest suspect cervical LN served as the reference method. In the same scans, maximum orthogonal diameters were measured using the distance measurement tool in standard visualization software in axial and coronal sections. From these diameters, approximate volumes were calculated using the cubic and ellipsoid formula. A second segmentation volumetry was performed in contrast enhanced radiotherapy-planning CT scans obtained prior to primary concurrent RCT 24 days (+/- 13 days) following the initial diagnostic CT scans. Intraclass correlation coefficients and Bland-Altman analyses were used to compare results. RESULTS: Slice-by-slice manual segmentation volumetry of primary and LN volumes revealed a lognormal distribution and ranged from 0 to 86 ml and 0 to 129 ml, respectively. Volume approximations in diagnostic CT scans with the ellipsoid formula resulted in an -8 % underestimation of tumor volumes (95 % CI -14 % to -1 %; p = 0.022) and an -18 % underestimation of suspect cervical LN volumes (95 % CI -25 % to -12 %; p = 0.001). Inter rater intraclass correlation for primaries was 0.95 (95 % CI +0.92 to +0.97; p = 0.001), and intra rater intraclass correlation was 0.99 (95 % CI +0.98 to +0.99; p = 0.001). The cubic formula resulted in pronounced overestimation of primary and LN volumes. Primary tumor volumes obtained by the second segmentation volumetry in radiotherapy-planning CT scans obtained on average 24 days following the initial volumetry resulted in larger primary tumor volumes (mean bias +28 %, 95 % CI +14 % to +41 %; p = 0.001). Tumor volume increase correlated with time between the diagnostic and planning CTs (r = 0.24, p = 0.05) and was approximately 1 % per day. DISCUSSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC using maximum orthogonal diameters underestimates volumes based on segmentation in multiple slices. Due to time difference and safety margins, segmented volumes in radiotherapy-planning CT scans tend to be larger than in diagnostic CT scans. CONCLUSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC are easily available from diagnostic CT scans. Volume estimates are applicable over a wide range of tumor and LN sizes and may be useful in clinical decision-making and oncologic research.

Safety of Radioembolization with (90)Yttrium Resin Microspheres Depending on Coiling or No-Coiling of Aberrant/High-Risk Vessels.

PURPOSE: To evaluate the safety of radioembolization (RE) with (90)Yttrium ((90)Y) resin microspheres depending on coiling or no-coiling of aberrant/high-risk vessels. MATERIALS AND METHODS: Early and late toxicity after 566 RE procedures were analyzed retrospectively in accordance with the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v3.0). For optimal safety, aberrant vessels were either coil embolized (n = 240/566, coiling group) or a more peripheral position of the catheter tip was chosen to treat right or left liver lobes (n = 326/566, no-coiling group). RESULTS: Clinically relevant late toxicities (≥ Grade 3) were observed in 1% of our overall cohort. The no-coiling group had significantly less "any" (P = 0.0001) or "clinically relevant" (P = 0.0003) early toxicity. There was no significant difference (P > 0.05) in delayed toxicity in the coiling versus the no-coiling group. No RE-induced liver disease was noted after all 566 procedures. CONCLUSION: RE with (90)Y resin microspheres is a safe and effective treatment option. Performing RE without coil embolization of aberrant vessels prior to treatment could be an alternative for experienced centers.

Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease.

PURPOSE: Diabetes mellitus type 2 (2DM) is associated with altered bone quality. In order to analyze associated changes on a molecular level, we investigated the gene expression of key factors of osteoblast metabolism in type 2 diabetics. METHODS: Total mRNA and protein of bone samples from 2DM patients and non-diabetic patients were isolated, and subsequently, reverse transcription polymerase chain reaction (RT-PCR) or Western blot was performed. Furthermore, pro- and anti-inflammatory serum cytokine levels were determined using a cytokine array. RESULTS: Expression of runt-related transcription factor 2 (RUNX2) was increased by 53 %. Expression of the bone sialoproteins, secreted phosphoprotein 1 (SPP1; osteopontin), and integrin-binding sialoprotein (IBSP), was elevated by more than 50 %, and activating transcription factor 4 (ATF4) expression was 13 % lower in the investigated diabetes group compared to the control group. Similarly, the expression of versican (VCAN) and decorin (DCN) was upregulated twofold in the diabetic group. At the same time, 2DM patients and controls show alterations in pro- and anti-inflammatory cytokine levels in the serum. CONCLUSIONS: This study identifies considerable changes in the expression of transcription factors and extracellular matrix (ECM) components of bone in 2DM patients. Furthermore, the analysis of key differentiation factors of osteoblasts revealed significant alterations in gene expression of these factors, which may contribute to the dysregulation of energy metabolism in 2DM.

Short communication: Is consumption of a cheese rich in angiotensin-converting enzyme-inhibiting peptides, such as the Norwegian cheese Gamalost, associated with reduced blood pressure?

Epidemiological and clinical studies have shown that angiotensin-converting enzyme (ACE)-inhibiting peptides derived from dairy products may decrease blood pressure. These peptides have been identified in many cheeses, and Gamalost, a traditional Norwegian cheese, is particularly rich in these peptides. The aim of this cross-sectional study was to examine whether frequency of Gamalost intake was associated with blood pressure in a Norwegian population sample. Blood pressure and other clinical measurements, including the factors of metabolic syndrome, were obtained from 168 participants (56% female, mean age = 51 yr) who completed a questionnaire about dietary habits and other health-related factors. Mean Gamalost intake was 2 servings per week. The prevalence of hypertension was 23.8% in the population, with mean systolic and diastolic blood pressures of 128 and 78 mmHg, respectively. Intake of Gamalost was inversely associated with systolic blood pressure. Each increase in frequency unit of Gamalost intake corresponded to a reduction in systolic blood pressure of 0.72 mmHg, after controlling for sex, age, education, waist circumference, physical activity, smoking status, and dairy food intake. Results from this study indicate that consumption of Gamalost (or other foods rich in ACE-inhibiting peptides) may reduce blood pressure.

Radioembolization with Yttrium-90 microspheres (SIRT) in pancreatic cancer patients with liver metastases: efficacy, safety and prognostic factors.

OBJECTIVE: To analyze the clinical efficacy of (90)Y radioembolization in liver metastases from pancreatic cancer, to describe treatment toxicities and to identify biomarkers as predictors of outcome. METHODS: Data from 19 pancreatic cancer patients (9 females/10 males) who had received (90)Y radioembolization for metastatic liver disease between 06/2004 and 01/2011 were analyzed retrospectively. RESULTS: The median age at (90)Y radioembolization was 63 years (range 43-77). In 16 patients, previous palliative gemcitabine-based chemotherapy was given for metastatic disease. Objective response in the liver after (90)Y radioembolization was 47%. Median local progression-free survival in the liver was 3.4 months (range 0.9-45.0). Median overall survival (OS) was 9.0 months (range 0.9-53.0) and 1-year survival was 24%. Cox regression models for baseline biomarkers at (90)Y radioembolization revealed correlations of increased carbohydrate antigen 19-9 (p = 0.02) and C-reactive protein (p = 0.03) with shorter OS. Short-term adverse events (nausea, vomiting, fatigue, fever and abdominal pain) did not exceed grade 3. As long-term adverse events, liver abscesses, gastroduodenal ulceration, cholestasis and cholangitis, ascites and spleen infarction were observed. CONCLUSION: (90)Y radioembolization is able to induce an encouraging local response rate of liver metastases of pancreatic cancer patients. Most short-term toxicities are manageable; however, patients should be followed up carefully for severe long-term toxicities.

Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients.

PURPOSE: To retrospectively evaluate the overall survival, safety, and efficacy of metastatic uveal melanoma patients after radioembolization as salvage therapy. MATERIALS AND METHODS: Thirteen patients were treated with radioembolization of branches of the hepatic artery with resin-based yttrium-90 ((90)Y)-labelled microspheres. Twelve patients underwent a single application, and 1 patient underwent 4 interventions. Dosages from 644 to 2,450 MBq (mean activity 1,780) were applied. Treatment response was evaluated by way of liver magnetic resonance imaging and computed tomography (CT) as well as whole-body fluorodeoxyglucose positron emission tomography (PET)/CT with evaluation of percentage changes in SUV(max) before and at 2-3 months after therapy. Kaplan-Meier analysis was calculated to determine overall survival. RESULTS: Partial remission (PR) was observed in 8 (62 %), stable disease (SD) in 2 (15 %), and progressive disease (PD) in 3 (23 %) patients under terms of standard criteria and PR in 3 (23 %), SD in 3 (23 %), and PD in 7 (54 %) patients according to PET criteria. Neither RECIST nor PET criteria showed a significant difference in predicting overall survival (P = 0.12 and 0.11, respectively). Median survival time after radioembolization was 7 months. No acute toxicity with in-hospital morbidity was observed. One patient developed hepatomegaly, and 1 patient developed gastric ulceration. Throughout follow-up, progression of extrahepatic metastases was observed. CONCLUSION: Radioembolization may be a promising therapy in uveal melanoma patients with predominant hepatic metastases. At first follow-up, we observed PR or SD in 77 % patients under terms of standard criteria with an acceptable toxicity profile.

[SPECT/CT for staging and treatment monitoring in oncology. Applications in differentiated thyroid cancer and liver tumors]. / SPECT/CT zum initialen Staging und Therapiemonitoring in der Onkologie. Indikationen beim differenzierten Schilddrüsenkarzinom und bei Lebertumoren.

CLINICAL/METHODICAL ISSUE: Hybrid imaging of function and morphology has gained significant importance for lesion detection and treatment monitoring in oncology. In patients with differentiated thyroid carcinoma (DTC) a planar whole body scan is carried out after radioiodine therapy (RIT) for staging. However, due to limited spatial resolution the diagnostic accuracy of this scintigraphy method is impaired. Radioembolization utilizing (90)Yttrium loaded micro-spheres by selective internal radiotherapy (SIRT) allows a minor invasive therapy of primary and secondary liver tumors. In order to avoid side effects of the micro-spheres caused by an outflow into intestines, stomach or lungs, imaging the arteries supplying the liver has to be performed by means of technetium-99m macroaggregated albumin ((99m)Tc-MAA) and scintigraphy. The limited morphological information supplied by scintigraphy is again a challenge in treatment monitoring. STANDARD RADIOLOGICAL/NUCLEAR MEDICAL METHODS: (131)Iodine whole body scanning is used for staging in patients with DTC 3-4 days after ablation. Monitoring of the tumor marker thyroglobulin and selective radioiodine whole body scans are available for patients with a high risk profile in the further follow-up with imaging of the arteries supplying the liver by means of (99m)Tc-MAA scintigraphy in preparation of SIRT. METHODICAL INNOVATIONS: Single photon emission computed tomography/computed tomography (SPECT/CT) of the neck and thorax with a therapeutic activity of radioiodine for staging after ablation. Techniques include imaging of arteries supplying the liver by means of (99m)Tc-MAA SPECT/CT before SIRT and evaluation and quantification of the uptake of liver tumors, especially in comparison to the uptake of liver parenchyma by means of SPECT/CT. PERFORMANCE: Due to the integration of combined functional and morphological information SPECT/CT can be used to characterize the morphology and iodine uptake of lesions more accurately, resulting in optimized staging in patients with DTC in comparison to whole body iodine scans and SPECT/CT provides more accurate imaging of the arterial supply of the liver and of potential outflows of micro-spheres into other organs. SPECT/CT allows evaluation and quantification of the uptake of liver tumors. ACHIEVEMENTS: Improved postablative staging in patients with differentiated thyroid cancer by SPECT/CT in comparison to radioiodine whole body scans can be achieved. Improved planning and monitoring of SIRT therapies utilizing SPECT/CT leads to optimized therapeutic doses within liver lesions. PRACTICAL RECOMMENDATIONS: Integration of SPECT/CT into the clinical standard for postablative staging in patients with DTC is recommended as well as utilization of SPECT/CT during the planning process, for dose calculation and treatment monitoring of SIRT therapies.

[Importance of PET/CT for imaging of colorectal cancer]. / Stellenwert der PET/CT zur Bildgebung des kolorektalen Karzinoms.

CLINICAL/METHODICAL ISSUE: Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has emerged as a very useful imaging modality in the management of colorectal carcinoma. Data from the literature regarding the role of PET/CT in the initial diagnosis, staging, radiotherapy planning, response monitoring and surveillance of colorectal carcinoma is presented. Future directions and economic aspects are discussed. STANDARD RADIOLOGICAL METHODS: Computed tomography (CT), magnetic resonance imaging (MRI) and FDG-PET for colorectal cancer and endorectal ultrasound for rectal cancer. METHODICAL INNOVATIONS: Combined FDG-PET/CT. PERFORMANCE: While other imaging modalities allow superior visualization of the extent and invasion depth of the primary tumor, PET/CT is most sensitive for the detection of distant metastases of colorectal cancer. ACHIEVEMENTS: We recommend a targeted use of PET/CT in cases of unclear M staging, prior to metastasectomy and in suspected cases of residual or recurrent colorectal carcinoma with equivocal conventional imaging. The role of PET/CT in radiotherapy planning and response monitoring needs to be determined. Currently there is no evidence to support the routine use of PET/CT for colorectal screening, staging or surveillance. PRACTICAL RECOMMENDATIONS: To optimally exploit the synergy between morphologic and functional information, FDG-PET should generally be performed as an integrated FDG-PET/CT with a contrast-enhanced CT component in colorectal carcinoma.

[Gastroenteropancreatic neuroendocrine tumors: diagnosis and therapy in nuclear medicine]. / Neuroendokrine Tumoren des gastroenteropankreatischen Systems: Nuklearmedizinische Diagnostik und Therapie.

The over expression of somatostatin receptors (SSTR) in neuroendocrine tumors (NET) enables diagnosis and targeted therapy using radio-labelled somatostatin analogues. PET with (68)Ga-DOTATATE or (68)Ga-DOTATOC, both with a high affinity to the SSTR subtype 2, enables diagnosis of NET with a very high sensitivity and has a significant influence on the therapeutic management of patients with NET. In particular, therapy with (177)Lu-DOTATATE, which offers a considerably lower nephrotoxicity as compared to (90)Y-DOTATOC, has only few side effects and is usually well tolerated. Up to 46% of patients suffering from GEP-NET show a response to this therapy, which is able to mitigate tumour-related symptoms and significantly improve quality of life.

FDG-PET-CT and whole-body MRI for triage in patients planned for radioembolisation therapy.

PURPOSE: The purpose was to evaluate the potential of FDG-PET-CT and whole-body MRI (WB-MRI) as diagnostic triage methods for patients planned for radioembolisation of metastatic liver disease. MATERIALS AND METHODS: 135 patients with multifocal liver metastases were evaluated for potential palliative therapy with radioembolisation using 90-Yttrium microspheres. All patients were examined consecutively with FDG-PET-CT and WB-MRI for exclusion of relevant extra-hepatic tumor manifestations. All patients underwent 99mTc-albumine angiography followed by scintigraphy to exclude significant hepato-pulmonary shunting. RESULTS: Out of the 135 patients included into the pre-therapeutic diagnostic algorithm, 56% were eligible and received radioembolisation, while 44% could not be treated. In 91% the exclusion criteria was diagnosis of significant extra-hepatic metastatic disease. In 85% exclusion diagnosis was made concordantly by both FDG-PET-CT and WB-MRI, in 9% diagnosis was provided by PET-CT, in 6% by WB-MRI alone. Patient-based sensitivity for detection of extra-hepatic disease was 94% for PET-CT and 91% for WB-MRI. False-positive diagnosis of extrahepatic disease leading to exclusion for radioembolisation therapy was made in 2% of patients, in one patient by PET-CT and in one patient by WB-MRI alone. Overall, specificity for inclusion of radioembolisation therapy by combining both modalities was 99%. In 9% of patients angiographic diagnosis made radioembolisation impossible, in 7% solely the angiographic findings were decisive. CONCLUSION: Both FDG-PET-CT and WB-MRI are efficient diagnostic triage methods for patients planned for radioembolisation of liver metastases. Overall, FDG-PET-CT shows a trend to higher diagnostic accuracy compared to WB-MRI and may be used as imaging method of choice as a standalone examination. In combination, both modalities exhibited high sensitivity for the diagnosis of extra-hepatic tumor manifestations and result in high specificity.

[Hepatic metastases in CUP (cancer of unknown primary) and painful amaurosis]. / Hepatische Filiae bei CUP ("cancer of unknown primary") und schmerzhafter Amaurose.

A 63-year-old woman presented with a 9-month history of painful amaurosis of the left eye caused by hemophthalmos. She was already undergoing chemotherapy for histopathologically proven liver metastases caused by an assumed melanoma. The location of the primary tumor was unknown. Whole-body FDG-PET/CT staging identified a lesion with characteristically malignant uptake in the region of the left eye as the primary tumor. After enucleation, a primary uveal melanoma was verified that expressed the serological marker melanoma inhibitory activity (MIA). FDG-PET/CT was able to successfully align hepatic metastases due to CUP with local ophthalmologic diagnostic findings and led to a correct diagnosis.