Christian Furth

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.

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.

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.

68Ga-DOTATOC PET/CT of Neuroendocrine Tumors: Spotlight on the CT Phases of a Triple-Phase Protocol

The diagnostic value of neuroendocrine tumor (NET) imaging using PET with integrated CT is dependent on both components. This retrospective study assessed the value of the single CT phases of a triple-phase (early arterial, portal-venous inflow, and venous) CT protocol in comparison to 68Ga-DOTATOC PET in a masked reading. Methods: 68Ga-DOTATOC PET/CT examinations from 51 patients with known or suspected NET were included. Two readers assessed the data of PET and each of the 3 CT phases for NET lesions independently (using a 3-point score: 1 = benign, 2 = indeterminate, and 3 = malignant) and by consensus (using binary benign/malignant interpretation only). Only lesions within the field of the abdominal scan were evaluated. Clinical and imaging follow-up, histopathology (if available), and the decision of an interdisciplinary truth-panel served as a standard of reference. In addition to the calculation of standard statistical parameters (including general linear mixed models), interobserver reliability was estimated (Cohens κ). Results: Of 510 abdominal lesions observed, 354 were classified as malignant. Sensitivity was 77.1% for combined triple-phase CT, 53.4% for arterial CT, 66.1% for portal-venous CT, 66.9% for venous CT, and 72.8% for PET. The respective specificities were 85.3%, 92.9%, 92.3%, 89.7%, and 97.4%, and the respective accuracies were 79.6%, 65.5%, 74.1%, 73.9%, and 80.4%. Although arterial CT was found to be inferior to PET, portal-venous CT, and venous CT (P < 0.001), the differences between the other scans were not significant. Detection was exclusively by PET for 16.1% of lesions, by triple-phase CT for 20.3%, by arterial CT for 0.5%, by portal-venous CT for 3.9%, and by venous CT for 3.9%. Regarding interobserver reliability, the κ-value was 0.768 for PET, 0.391 for triple-phase CT, 0.577 for arterial CT, 0.583 for portal-venous CT, and 0.482 for venous CT. Conclusion: No CT phase can be omitted in NET imaging, and the triple-phase protocol continues to be strongly recommended also for PET/CT.

Predictive Value of Intratumoral 99mTc-Macroaggregated Albumin Uptake in Patients with Colorectal Liver Metastases Scheduled for Radioembolization with 90Y-Microspheres

90Y radioembolization is a promising therapy for patients with primary and secondary liver malignancies. Pretherapeutic assessment consists of hepatic angiography and 99mTc-macroaggregated albumin (99mTc-MAA) perfusion scintigraphy to estimate the liver-to-lung shunt and exclude extrahepatic 99mTc-MAA deposition. However, the predictive value of intratumoral 99mTc-MAA uptake remains unclear. Methods: One hundred four patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer were treated with 90Y radioembolization between December 2006 and December 2010. All of the patients underwent angiographic assessment and perfusion scintigraphy with 99mTc-MAA before lobar 90Y radioembolization. For inclusion, patients must have undergone pretherapeutic and follow-up MR imaging (6 wk and 3 mo after radioembolization, respectively). The degree of intratumoral 99mTc-MAA uptake was rated, and liver metastases were classified according to changes in tumor diameter on both an individual and a patient basis using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response at both time points, MAA uptake, and catheter position were then statistically analyzed in a linear and generalized linear mixed model at a significance level of 0.05 (P value). Results: Sixty-six patients with a total of 435 colorectal liver metastases (mean number of lesions ± SD, 6.6 ± 2.8; mean lesion size ± SD, 33.8 ± 21.2 mm; lesion size range, 10–154 mm) were included in this analysis. According to the patient-based analysis, 3 patients had partial response, 49 stable disease, and 6 progressive disease after 6 wk. After 3 mo, 5 patients showed partial response, 26 stable disease, and 17 progressive disease. There was no association of patient-based tumor response with overall 99mTc-MAA uptake (P = 0.172) or with catheter position (P = 0.6456). Furthermore, an interaction effect of 99mTc-MAA uptake and catheter position in relation to tumor response was not found (P = 0.512). Moreover, in lesion-based analysis according to RECIST 1.1 there was no association of tumor response with degree of 99mTc-MAA uptake, catheter position, or interaction of 99mTc-MAA uptake and catheter position (P = 0.339, 0.593, and 0.658, respectively). Conclusion: Response to 90Y radioembolization was found to be independent of the degree of 99mTc-MAA uptake. Therefore, therapy should not be withheld from patients with colorectal liver metastases lacking intratumoral 99mTc-MAA accumulation.

Impact of whole-body MRI and FDG-PET on staging and assessment of therapy response in a patient with Ewing sarcoma

In patients with Ewing sarcoma, precise staging is not only crucial for the therapeutic regimen but also for a reliable evaluation of response to therapy. We report on a 15‐year‐old girl with metastatic spread of a Ewing sarcoma who, apart from conventional staging by bone scan, chest X‐ray and CT, was subsidiary examined by FDG‐PET and whole‐body MRI before and after chemotherapy. Both modalities detected more bone lesions than the bone scan, which led to an altered strategy for radiotherapy. Both examinations might be a great asset to stage‐adjusted therapy regimens, ultimately influencing patient outcome. Pediatr Blood Cancer 2006; 47:607–611.

Blinded-read of bone scintigraphy: the impact on diagnosis and healing time for stress injuries with emphasis on the foot.

Aim: This study evaluated the use of bone scintigraphy (BS) for the diagnosis of stress fractures in athletes and its validity for the prediction of healing time, with a focus on foot injuries. Methods: In our retrospective study, 84 athletes with a total of 93 suspected stress fractures (foot, n = 66; others, n = 27) were included. A blinded-read of BS was performed by 3 observers. The standard of reference was established by an interdisciplinary truth-panel using all imaging data (scintigraphic, radiographic, and magnetic resonance imaging) and follow-up data (>12 month). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosing stress fractures were calculated. Stress injuries were rated according to a 5-point grading score (0–4) and associated to the healing time. Results: For the diagnosis of stress injuries (n = 50/93), mean sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 97.3%, 67.4%, 77.7%, 95.6%, and 83.5%, respectively. Interobserver analysis showed a high agreement between all 3 readers (mean &kgr; = 0.83). In univariate analysis healing time of grade 3 to 4 stress injuries was significantly higher (median, 87 days; interquartile range, 69–132 days) compared with grade 1 to 2 lesions (median, 63 days; interquartile range, 43–95 days; P = 0.0067). Moreover, healing time of scintigraphic high grade stress injuries was significantly longer in a general linear model with adjustment for cofactors (grade, 3–4 vs. 1–2; P = 0.033). Conclusions: BS is a sensitive and reliable method for the diagnosis of stress injuries. In addition, the simplified classification for mild and severe stress injuries allows an estimation of healing time.

The influence of different signal-to-background ratios on spatial resolution and F18-FDG-PET quantification using point spread function and time-of-flight reconstruction

BackgroundF18-fluorodeoxyglucose positron-emission tomography (FDG-PET) reconstruction algorithms can have substantial influence on quantitative image data used, e.g., for therapy planning or monitoring in oncology. We analyzed radial activity concentration profiles of differently reconstructed FDG-PET images to determine the influence of varying signal-to-background ratios (SBRs) on the respective spatial resolution, activity concentration distribution, and quantification (standardized uptake value [SUV], metabolic tumor volume [MTV]).MethodsMeasurements were performed on a Siemens Biograph mCT 64 using a cylindrical phantom containing four spheres (diameter, 30 to 70 mm) filled with F18-FDG applying three SBRs (SBR1, 16:1; SBR2, 6:1; SBR3, 2:1). Images were reconstructed employing six algorithms (filtered backprojection [FBP], FBP + time-of-flight analysis [FBP + TOF], 3D-ordered subset expectation maximization [3D-OSEM], 3D-OSEM + TOF, point spread function [PSF], PSF + TOF). Spatial resolution was determined by fitting the convolution of the object geometry with a Gaussian point spread function to radial activity concentration profiles. MTV delineation was performed using fixed thresholds and semiautomatic background-adapted thresholding (ROVER, ABX, Radeberg, Germany).ResultsThe pairwise Wilcoxon test revealed significantly higher spatial resolutions for PSF + TOF (up to 4.0 mm) compared to PSF, FBP, FBP + TOF, 3D-OSEM, and 3D-OSEM + TOF at all SBRs (each P < 0.05) with the highest differences for SBR1 decreasing to the lowest for SBR3. Edge elevations in radial activity profiles (Gibbs artifacts) were highest for PSF and PSF + TOF declining with decreasing SBR (PSF + TOF largest sphere; SBR1, 6.3%; SBR3, 2.7%). These artifacts induce substantial SUVmax overestimation compared to the reference SUV for PSF algorithms at SBR1 and SBR2 leading to substantial MTV underestimation in threshold-based segmentation. In contrast, both PSF algorithms provided the lowest deviation of SUVmean from reference SUV at SBR1 and SBR2.ConclusionsAt high contrast, the PSF algorithms provided the highest spatial resolution and lowest SUVmean deviation from the reference SUV. In contrast, both algorithms showed the highest deviations in SUVmax and threshold-based MTV definition. At low contrast, all investigated reconstruction algorithms performed approximately equally. The use of PSF algorithms for quantitative PET data, e.g., for target volume definition or in serial PET studies, should be performed with caution - especially if comparing SUV of lesions with high and low contrasts.

SUV-measurements and patient-specific corrections in pediatric Hodgkin-lymphoma: Is there a benefit for PPV in early response assessment by FDG-PET?†

To evaluate the influence of different SUV‐measurements and patient‐specific corrections thereof on the positive predictive value (PPV) of FDG‐PET in pediatric Hodgkin lymphoma (pHL) using SUV‐based response assessment.

Intrahepatic Activity Distribution in Radioembolization with Yttrium-90-Labeled Resin Microspheres Using the Body Surface Area Method--A Less than Perfect Model.

PURPOSE To retrospectively assess the influence of the parameters of the body surface area (BSA) method in hepatic radioembolization using yttrium-90-labeled microspheres on the determination of the prescribed activity. MATERIALS AND METHODS Data from 283 consecutive patients treated with radioembolization (BSA method) were included. For interindividual comparisons, activity concentrations (ACs; MBq/mL) were calculated for each liver. The impact of the BSA method parameters was assessed by analysis of variance and pairwise t test with Bonferroni-Holm correction. RESULTS Prescribed activity was 1.01-2.71 GBq, with BSA, liver volume (LV), tumor burden, and the liver-lung shunt reduction factor (LLS RF) being significant contributing factors to the AC (all P < .0001, analysis of variance). BSA and LV correlated only moderately (ρ = 0.46, P < .0001). Compared with base activity defined by the BSA (median = 1.67 GBq; range, 1.20-2.32 GBq), the activity contribution of tumor burden was small (median = 150 MBq; range, 3-800 MBq). Resulting activities were reduced according to LLS RF by 20% in 12.4% and by 40% in 3.5% of patients. AC was significantly (up to 56%) lower in association with larger LV than in small LV (LV < 1,500 mL vs ≥ 2,500 mL, P < .0001). CONCLUSIONS In the BSA model, BSA and LV showed only a moderate correlation, resulting in a significantly lower AC in patients with larger livers. Tumor burden percentage contributed little to the prescribed activity because the BSA model did not account for actual LVs and tumor volumes. These inaccuracies may potentially result in underdosage in patients with larger livers, especially if further LLS RF needs to be applied.