The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management.

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Purpose: Early identification of aggressive disease could improve decision support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-positron emission tomography (PET) before PRRT was analyzed. Procedures: Thirty-one patients with G1/G2 pNET were enrolled (G2, n = 23/31). Prior to PRRT with [ 177 Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET computed tomography was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV mean/max ), imaging-based TF, and clinical parameters (Ki67, CgA) for prediction of both progression-free survival (PFS) and overall survival (OS) after PRRT were evaluated. Correspondence to: Ralph Bundschuh; e-mail: ralph.bundschuh@ukbonn.deResults: Within a median follow-up of 3.7 years, tumor progression was detected in 21 patients (median, 1.5 years) and 13/31 deceased (median, 1.9 years). In ROC analysis, the TF entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff = 6.7, AUC = 0.71, p = 0.02). Of note, increasing entropy could predict a longer survival (9 6.7, OS = 2.5 years, 17/31), whereas less voxel-based derangement portended inferior outcome (G 6.7, OS = 1.9 years, 14/31). These findings were supported in a G2 subanalysis (9 6.9, OS = 2.8 years, 9/23 vs. G 6.9, OS = 1.9 years, 14/23). Kaplan-Meier analysis revealed a significant distinction between high-and low-risk groups using entropy (n = 31, p G 0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n = 31, p = 0.04). Ki67 was negatively associated with PFS (p = 0.002); however, SUV mean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.

Background-Myocardial infarction (MI) triggers a systemic inflammatory response which determines subsequent healing.Experimentally, cardiac positron emission tomography and magnetic resonance imaging have been used successfully to obtain mechanistic insights. We explored the translational potential in patients early after MI. Methods and Results-Positron emission tomography/computed tomography and cardiac magnetic resonance were performed in 15 patients <7 days after first MI. Cardiac magnetic resonance showed regional transmural late gadolinium enhancement and edema exceeding the area of late gadolinium enhancement. Using F-18 deoxyglucose with heparin pretreatment, metabolic rate of glucose (MRGlc)

BackgroundStandardized treatment in pediatric patients with Hodgkin’s lymphoma (HL) follows risk stratification by tumor stage, erythrocyte sedimentation rate and tumor bulk. We aimed to identify quantitative parameters from pretherapeutic FDG-PET to assist prediction of response to induction chemotherapy.MethodsRetrospective analysis in 50 children with HL (f:18; m:32; median age, 14.8 [4–18] a) consecutively treated according to EuroNet-PHL-C1 (n = 42) or -C2 treatment protocol (n = 8). Total metabolic tumor volume (MTV) in pretherapeutic FDG-PET was defined using a semi-automated, background-adapted threshold. Metabolic (SUVmax, SUVmean, SUVpeak, total lesion glycolysis [MTV*SUVmean]) and heterogeneity parameters (asphericity [ASP], entropy, contrast, local homogeneity, energy, and cumulative SUV-volume histograms) were derived. Early response assessment (ERA) was performed after 2 cycles of induction chemotherapy according to treatment protocol and verified by reference rating. Prediction of inadequate response (IR) in ERA was based on ROC analysis separated by stage I/II (1 and 26 patients) and stage III/IV disease (7 and 16 patients) or treatment group/level (TG/TL) 1 to 3.ResultsIR was seen in 28/50 patients (TG/TL 1, 6/12 patients; TG/TL 2, 10/17; TG/TL 3, 12/21). Among all PET parameters, MTV best predicted IR; ASP was the best heterogeneity parameter. AUC of MTV was 0.84 (95%-confidence interval, 0.69–0.99) in stage I/II and 0.86 (0.7–1.0) in stage III/IV. In patients of TG/TL 1, AUC of MTV was 0.92 (0.74–1.0); in TG/TL 2 0.71 (0.44–0.99), and in TG/TL 3 0.85 (0.69–1.0). Patients with high vs. low MTV had IR in 86 vs. 0% in TG/TL 1, 80 vs. 29% in TG/TL 2, and 90 vs. 27% in TG/TL 3 (cut-off, > 80 ml, > 160 ml, > 410 ml).ConclusionsIn this explorative study, high total MTV best predicted inadequate response to induction therapy in pediatric HL of all pretherapeutic FDG-PET parameters – in both low and high stages as well as the 3 different TG/TL.Trial registrationEthics committee number: EA2/151/16 (retrospectively registered).Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4432-4) contains supplementary material, which is available to authorized users.

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