Ingo G. Steffen

Positron Emission Tomography for Staging of Pediatric Sarcoma Patients: Results of a Prospective Multicenter Trial

PURPOSE The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients. PATIENTS AND METHODS In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 +/- 12 months), and histopathology and was determined by an interdisciplinary tumor board. RESULTS FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001). CONCLUSION In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.

Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients

IntroductionNeuron specific enolase (NSE) has been proven effective in predicting neurological outcome after cardiac arrest with a current cut off recommendation of 33 μg/l. However, most of the corresponding studies were conducted before the introduction of mild therapeutic hypothermia (MTH). Therefore we conducted a study investigating the association between NSE and neurological outcome in patients treated with MTHMethodsIn this prospective observational cohort study the data of patients after cardiac arrest receiving MTH (n = 97) were consecutively collected and compared with a retrospective non-hypothermia (NH) group (n = 133). Serum NSE was measured 72 hours after admission to ICU. Neurological outcome was classified according to the Pittsburgh cerebral performance category (CPC 1 to 5) at ICU discharge.ResultsNSE serum levels were significantly lower under MTH compared to NH in univariate analysis. However, in a linear regression model NSE was affected significantly by time to return of spontaneous circulation (ROSC) and ventricular fibrillation rhythm but not by MTH. The model for neurological outcome identified NSE, NSE*MTH (interaction) as well as time to ROSC as significant predictors. Receiver Operating Characteristic (ROC) analysis revealed a higher cutoff value for unfavourable outcome (CPC 3 to 5) with a specificity of 100% in the hypothermia group (78.9 μg/l) compared to the NH group (26.9 μg/l).ConclusionsRecommended cutoff levels for NSE 72 hours after ROSC do not reliably predict poor neurological outcome in cardiac arrest patients treated with MTH. Prospective multicentre trials are required to re-evaluate NSE cutoff values for the prediction of neurological outcome in patients treated with MTH.

Early and Late Therapy Response Assessment With [18F]Fluorodeoxyglucose Positron Emission Tomography in Pediatric Hodgkin's Lymphoma: Analysis of a Prospective Multicenter Trial

PURPOSE In adult Hodgkins lymphoma (HL) risk stratification after early therapy response assessment with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) seems to allow tailoring therapy with less toxicity for patients with adequate metabolic response. This study delivers the first prospective data on the potential of FDG-PET for response assessment in pediatric HL. PATIENTS AND METHODS FDG-PET was performed in 40 pediatric HL patients before polychemotherapy (PET-1), after two cycles of polychemotherapy (PET-2), and after completion of polychemotherapy (PET-3). Mean follow-up was 46 months (range, 26 to 72 months). RESULTS At early and late response assessment, the proportion of PET-negative patients was significantly higher compared with those patients with negative findings in conventional imaging methods (CIMs; PET-2, 26 of 40 v CIM-2, one of 40; P < .001; PET-3, 21 of 29 v CIM-3, four of 29; P < .001). Sensitivity and negative predictive value were 100% for early and late therapy response assessment by PET. Both patients suffering a relapse during follow-up were identified by PET-2/3, whereas one of these patients was not detected by CIM-3. PET was superior to CIMs with regard to specificity in early and late therapy response assessment (68% v 3%, and 78% v 11%, respectively; both P < .001). Specificity of early therapy response assessment by PET was improved to 97% by quantitative analysis of maximal standardized uptake value reduction using a cutoff value of 58%. CONCLUSION Pediatric HL patients with a negative PET in response assessment have an excellent prognosis while PET-positive patients have an increased risk for relapse.

Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls

IntroductionPersistent coma is a common finding after cardiac arrest and has profound ethical and economic implications. Evidence suggests that therapeutic hypothermia improves neurological outcome in these patients. In this analysis, we investigate whether therapeutic hypothermia influences the length of intensive care unit (ICU) stay and ventilator time in patients surviving out-of-hospital cardiac arrest.MethodsA prospective observational study with historical controls was conducted at our medical ICU. Fifty-two consecutive patients (median age 62.6 years, 43 males, 34 ventricular fibrillation) submitted to therapeutic hypothermia after out-of-hospital cardiac arrest were included. They were compared with a historical cohort (n = 74, median age 63.8 years, 53 males, 43 ventricular fibrillation) treated in the era prior to hypothermia treatment. All patients received the same standard of care. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. Univariate analyses and multiple regression models were used.ResultsIn survivors, therapeutic hypothermia and baseline disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] score) were both found to significantly influence ICU stay and ventilator time (all P < 0.01). ICU stay was shorter in survivors receiving therapeutic hypothermia (median 14 days [interquartile range (IQR) 8 to 26] versus 21 days [IQR 15 to 30] in the control group; P = 0.017). ICU length of stay and time on ventilator were prolonged in patients with CPC 3 or 4 compared with patients with CPC 1 or 2 (P = 0.003 and P = 0.034, respectively). Kaplan-Meier analysis showed improved probability for 1-year survival in the hypothermia group compared with the controls (log-rank test P = 0.013).ConclusionTherapeutic hypothermia was found to significantly shorten ICU stay and time of mechanical ventilation in survivors after out-of-hospital cardiac arrest. Moreover, profound improvements in both neurological outcome and 1-year survival were observed.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

PurposeThe objective of this study was to evaluate positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.MethodsFDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.ResultsFDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (∆SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (∆SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.ConclusionFDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Evaluation of the potential of PET-MRI fusion for detection of liver metastases in patients with neuroendocrine tumours

AbstractObjectivesThis study was performed to assess the role of retrospective PET-MRI fusion with Ga-68-DOTA(0)-Phe(1)-Tyr(3)-octreotide (Ga-68-DOTATOC) PET and Gd-EOB-DTPA MRI in the detection of hepatic metastases from neuroendocrine tumours (NET).MethodsTwenty-two consecutive patients with suspected liver metastases from histopathologically proven NET were examined with Gd-EOB-DTPA MRI and multiphase contrast-enhanced Ga-68-DOTATOC PET/CT. PET and MRI images were retrospectively fused using commercially available software. Two physicians experienced in nuclear medicine and radiology analysed the images to assess diagnostic confidence and characterise liver lesions.ResultsA total of 181 lesions were detected. PET-MRI showed a sensitivity of 91.2% (significantly superior to PET/CT; P < 0.05) and a specificity of 95.6% (significantly superior to MRI; P < 0.05). PET/CT had a sensitivity of 73.5% and a specificity of 88.2%. MRI had a sensitivity of 87.6% and a specificity of 86.8%. The area under the curve was 0.98 for PET-MRI, 0.96 for MRI, and 0.89 for PET/CT (P < 0.05).ConclusionsRetrospectively fused PET-MRI was superior to multiphase contrast-enhanced Ga-68-DOTATOC PET/CT and Gd-EOB-DTPA MRI in the detection of NET liver metastases. It was more sensitive than PET/CT and more specific than MRI. Fused PET-MRI therefore seems well suited for surgical and interventional treatment planning of NET liver metastases.Key Points• Ga-68-DOTATOC PET–Gd-EOB-DTPA MRI fusion can improve imaging of liver metastases of neuroendocrine tumours.• This technique appears more sensitive than PET/CT for staging NET hepatic metastases. • Ga-68-DOTATOC PET–Gd-EOB-DTPA MRI fusion is more specific than MRI alone.

Asphericity of pretherapeutic tumour FDG uptake provides independent prognostic value in head-and-neck cancer

AbstractObjectiveTo propose a novel measure, namely the ‘asphericity’ (ASP), of spatial irregularity of FDG uptake in the primary tumour as a prognostic marker in head-and-neck cancer.MethodsPET/CT was performed in 52 patients (first presentation, n = 36; recurrence, n = 16). The primary tumour was segmented based on thresholding at the volume-reproducible intensity threshold after subtraction of the local background. ASP was used to characterise the deviation of the tumour’s shape from sphere symmetry. Tumour stage, tumour localisation, lymph node metastases, distant metastases, SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were also considered. The association of overall (OAS) and progression-free survival (PFS) with these parameters was analysed.ResultsCox regression revealed high SUVmax [hazard ratio (HR) = 4.4/7.4], MTV (HR = 4.6/5.7), TLG (HR = 4.8/8.9) and ASP (HR = 7.8/7.4) as significant predictors with respect to PFS/OAS in case of first tumour manifestation. The combination of high MTV and ASP showed very high HRs of 22.7 for PFS and 13.2 for OAS. In case of recurrence, MTV (HR = 3.7) and the combination of MTV/ASP (HR = 4.2) were significant predictors of PFS.ConclusionsASP of pretherapeutic FDG uptake in the primary tumour improves the prediction of tumour progression in head-and-neck cancer at first tumour presentation.Key Points•Asphericity (ASP) characterises the spatial heterogeneity of FDG uptake in tumours • ASP is a promising prognostic parameter in head-and-neck cancer • ASP is useful for identification of high-risk patients with head-and-neck cancer

Contribution of 68Ga-DOTATOC PET/CT to Target Volume Delineation of Skull Base Meningiomas Treated With Stereotactic Radiation Therapy

PURPOSE To investigate the potential impact of 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) in addition to magnetic resonance imaging (MRI) and computed tomography (CT) for retrospectively assessing the gross tumor volume (GTV) delineation of meningiomas of the skull base in patients treated with fractionated stereotactic radiation therapy (FSRT). METHODS AND MATERIALS The study population consisted of 48 patients with 54 skull base meningiomas, previously treated with FSRT. After scans were coregistered, the GTVs were first delineated with MRI and CT data (GTVMRI/CT) and then by PET (GTVPET) data. The overlapping regions of both datasets resulted in the GTVcommon, which was enlarged to the GTVfinal by adding volumes defined by only one of the complementary modalities (GTVMRI/CT-added or GTVPET-added). We then evaluated the contribution of conventional imaging modalities (MRI, CT) and 68Ga-DOTATOC-PET to the GTVfinal, which was used for planning purposes. RESULTS Forty-eight of the 54 skull base lesions in 45 patients showed increased 68Ga-DOTATOC uptake and were further analyzed. The mean GTVMRI/CT and GTVPET were approximately 21 cm3 and 25 cm3, with a common volume of approximately 15 cm3. PET contributed a mean additional GTV of approximately 1.5 cm3 to the common volume (16%±34% of the GTVcommon). Approximately 4.5 cm3 of the GTVMRI/CT was excluded from the contribution to the common volume. The resulting mean GTVfinal was significantly smaller than both the GTVMRI/CT and the GTVPET. Compared with the initial GTVMRI/CT, the addition of 68Ga-DOTATOC-PET resulted in more than 10% modification of the size of the GTVfinal in 32 (67%) meningiomas CONCLUSIONS 68Ga-DOTATOC-PET/CT seems to improve the target volume delineation in skull base meningiomas, often leading to a reduction of GTV compared with results from conventional imaging (MRI and CT).

Size determination and response assessment of liver metastases with computed tomography—Comparison of RECIST and volumetric algorithms

OBJECTIVE To compare different three-dimensional volumetric algorithms (3D-algorithms) and RECIST for size measurement and response assessment in liver metastases from colorectal and pancreatic cancer. METHODS The volumes of a total of 102 liver metastases in 45 patients (pancreatic cancer, n=22; colon cancer, n=23) were estimated using three volumetric methods (seeded region growing method, slice-based segmentation, threshold-based segmentation) and the RECIST 1.1 method with volume calculation based on the largest axial diameter. Each measurement was performed three times by one observer. All four methods were applied to follow-up on 55 liver metastases in 29 patients undergoing systemic treatment (median follow-up, 3.5 months; range, 1-10 months). Analysis of variance (ANOVA) with post hoc tests was performed to analyze intraobserver variability and intermethod differences. RESULTS ANOVA showed significant higher volumes calculated according to the RECIST guideline compared to the other measurement methods (p<0.001) with relative differences ranging from 0.4% to 41.1%. Intraobserver variability was significantly higher (p<0.001) for RECIST and threshold based segmentation (3.6-32.8%) compared with slice segmentation (0.4-13.7%) and seeded region growing method (0.6-10.8%). In the follow-up study, the 3D-algorithms and the assessment following RECIST 1.1 showed a discordant classification of treatment response in 10-21% of the patients. CONCLUSIONS This study supports the use of volumetric measurement methods due to significant higher intraobserver reproducibility compared to RECIST. Substantial discrepancies in tumor response classification between RECIST and volumetric methods depending on applied thresholds confirm the requirement of a consensus concerning volumetric criteria for response assessment.

Multislice computed tomography using a triple-phase contrast protocol for preoperative assessment of hepatic tumor load in patients with hepatocellular carcinoma before liver transplantation.

For evaluation of triple‐phase multislice computed tomography (CT) for assessment of hepatocellular carcinoma (HCC) before liver transplantation. All HCC patients who underwent liver transplantation at our institution between 2001 and 2006 and had contrast‐enhanced abdominal 4‐/16‐slice CT [unenhanced, arterial (20 s delay), portal venous (40 s), and venous (80 s) scan] within 100 days before transplantation were enrolled retrospectively. CT data were reviewed by two observers. Results were correlated to histopathologic findings by means of a lesion‐by‐lesion evaluation. Thirty‐two patients with 76 HCC‐lesions were included. The lesion‐based sensitivity of observer 1 and 2 was 78% (59/76) and 83% (63/76) (false positives, n = 6 and n = 10). The sensitivity of observer 1/2 was 89%/95% for lesions >20 mm (n = 37), 94% for lesions 11–20 mm (n = 18), and 43%/53% for lesions <10 mm (n = 21). The mean detection rates of unenhanced, arterial, portal venous, and venous phase scans were 30%, 74%, 59%, and 40%. All detected lesions were visible on arterial and/or portal venous scans (arterial only, 24%; portal venous only, 9%). Arterial and portal venous phase scans are the strongest contributors to the high detection rate of triple‐phase multislice‐CT in HCC. However, the detection of small HCC measuring <10 mm and false positive findings remains a challenge.