Juri Ruf

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.

Detection of Recurrent Pancreatic Cancer: Comparison of FDG-PET with CT/MRI

Objective: To determine the value of fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the detection of recurrent pancreatic cancer in comparison to computed tomography (CT) and magnetic resonance imaging (MRI). Methods: Thirty-one patients with suspected recurrence after surgery were included. Inclusion criteria were sudden weight loss, pain or increased CA 19-9 levels. FDG-PET was performed in all patients. After visual analysis, maximal standardized uptake values (SUVmax) were determined by placing regions of interest on the pancreas bed. Additionally, all patients underwent contrast-enhanced multidetector CT (n = 14) or MR (n = 17) imaging. Positive findings at FDG-PET or CT/MRI were compared to follow-up. Results: All patients relapsed. Of 25 patients with local recurrences upon follow-up, initial imaging suggested relapse in 23 patients. Of these, FDG-PET detected 96% (22/23) and CT/MRI 39% (9/23). Local SUVmax ranged from 2.26 to 16.9 (mean, 6.06). Among 12 liver metastases, FDG-PET detected 42% (5/12). CT/MRI detected 92% (11/12) correctly. Moreover, 7/9 abdominal lesions were malignant upon follow-up of which FDG-PET detected 7/7 and CT/MR detected none. Additionally, FDG-PET detected extra-abdominal metastases in 2 patients. Conclusion: In patients suspected of pancreatic cancer relapse; FDG-PET reliably detected local recurrences, whereas CT/MRI was more sensitive for the detection of hepatic metastases. Furthermore, FDG-PET proved to be advantageous for the detection of nonlocoregional and extra-abdominal recurrences.

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.

Impact of SPECT and integrated low-dose CT after radioiodine therapy on the management of patients with thyroid carcinoma.

AimTo determine the value of single photon emission computed tomography (SPECT) with integrated low-dose computed tomography (CT) for the interpretation of inconclusive foci in planar 131I whole-body scans after radioiodine therapy. MethodsTwenty-five patients with inconclusive findings in planar scanning after ablative radioiodine therapy (3.7 GBq 131I) due to differentiated thyroid cancer were included. SPECT/CT of the region in question was performed with the Millennium VG Hawkeye (GE Medical Systems). SPECT with and without CT fusion were evaluated by two blinded independent nuclear medicine physicians in a consensus reading (including visual plausibility control). Each focus was judged according to its topographical assignment and clinical interpretation. With regard to therapeutic relevance, this information was evaluated in a focus based and patient based analysis. All evaluations used a binary ranking system. Focus assignments were compared to clinical and imaging follow-up. ResultsForty-one lesions were observed in 25 patients. According to follow-up, 17/41 (41%) foci were caused by thyroid residue, 13/41 (32%) were caused by metastases, and 11/41 (27%) were not malignant. Of these foci, a SPECT/CT consensus reading assigned 39 (95%) correctly, as fused images of two foci did not pass the visual plausibility control (excluding one patient due to misregistration). For the remaining 39 foci, improved anatomical assignment by SPECT/CT was seen in 17/39 (44%) cases. ConclusionsThe changed interpretation of 15/39 (38%) foci would have been relevant for therapy in the focus based analysis. In the patient based analysis the information was still therapeutically relevant in 6/24 (25%) patients. Furthermore, plausibility control is also crucial in SPECT/CT image fusion in order to rule out artifacts.

Impact of Multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors.

Aim: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). Methods: The 68Ga-DOTATOC-PET/CT data of 66 patients (31 male, 35 female; age: 29–79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. Results: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). Conclusion:68Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended.

Diagnosis of neuroendocrine tumours by retrospective image fusion: is there a benefit?

This study evaluated the use of image fusion in the preoperative staging of neuroendocrine tumors (NET) of the pancreas and the gastrointestinal tract (GIT). Thirty-eight patients suffering from a metastasized NET with location of the primary in the pancreas (n=15) or the GIT (n=23) were examined by somatostatin receptor scintigraphy (SRS) and computed tomography (CT). Consecutive image registration and fusion were performed using custom-built software integrated in AVS/Express (Advanced Visual Systems, Waltham, MA, USA). Registration was performed by a voxel-based algorithm based on normalized mutual information. Image fusion was feasible in 36/38 patients. A total of 87 foci were assigned to anatomical regions (e.g. gut, pancreas, liver, lymph node or others) by two independent observers in both SRS and SRS/CT fusion images. The assignments used a binary ranking system (1=”definite”, 0=”not definite”). These results were then retrospectively compared to the classification of the foci, based on postoperative histology or clinical follow-up. Imaging by SRS allowed a definite anatomical assignment in 57% (50/87) and 61% (53/87) of all lesions in the case of observers A and B, respectively. Image fusion improved the topographic assignment to 91% (79/87) and to 93% (81/87). The number classified as “definite” by both observers increased from 54% (47/87) to 86% (77/87). The increase in definite assignments was highly significant for both observers (P<0.0001 for each). In the case of foci classified as liver metastases, image fusion allowed improved assignment to the corresponding liver segment from 45% (18/40) to 98% (39/40) and from 58% (23/40) to 100% (40/40) by observers A and B, respectively. Furthermore, the improved assignment of foci classified as lesions by image fusion was relevant for therapy in 7/36 patients (19%). Therefore, the image fusion technique presented herein appears to be a very useful method for clinical routine.

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.

Value of image fusion using single photon emission computed tomography with integrated low dose computed tomography in comparison with a retrospective voxel-based method in neuroendocrine tumours

The objective was the evaluation of single photon emission computed tomography (SPECT) with integrated low dose computed tomography (CT) in comparison with a retrospective fusion of SPECT and high-resolution CT and a side-by-side analysis for lesion localisation in patients with neuroendocrine tumours. Twenty-seven patients were examined by multidetector CT. Additionally, as part of somatostatin receptor scintigraphy (SRS), an integrated SPECT–CT was performed. SPECT and CT data were fused using software with a registration algorithm based on normalised mutual information. The reliability of the topographic assignment of lesions in SPECT–CT, retrospective fusion and side-by-side analysis was evaluated by two blinded readers. Two patients were not enrolled in the final analysis because of misregistrations in the retrospective fusion. Eighty-seven foci were included in the analysis. For the anatomical assignment of foci, SPECT–CT and retrospective fusion revealed overall accuracies of 91 and 94% (side-by-side analysis 86%). The correct identification of foci as lymph node manifestations (n=25) was more accurate by retrospective fusion (88%) than from SPECT–CT images (76%) or by side-by-side analysis (60%). Both modalities of image fusion appear to be well suited for the localisation of SRS foci and are superior to side-by-side analysis of non-fused images especially concerning lymph node manifestations.

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.