Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

Ezziddin, Samer; Khalaf, Feras; Vanezi, Maria; Haslerud, Torjan; Mayer, Karin; Zreiqat, Abdullah Al; Willinek, Winfried A.; Biersack, Hans‐Jürgen; Sabet, Amir

doi:10.1007/s00259-013-2677-3

Cited by 169 publications

(133 citation statements)

References 43 publications

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“…A recent series reported on [67] pNETs patients with inoperable metastatic disease treated with 177 Lu-octreotate showing a partial response rate of 60.3 % with stabilization of disease in 13.2 % of cases. In the same study, the median progression-free survival and overall survival were 34 and 53 months, respectively [93]. Similar findings were reported by other authors [94][95][96], suggesting a potential role for this therapy in the setting of advanced pNETs.…”

Section: Somatostatin Analogues and Peptide Receptor Radiotherapysupporting

confidence: 87%

Pancreatic Neuroendocrine Tumors: an Update

2015

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Pancreatic neuroendocrine tumors (pNETs) are rare and comprise only 1-2 % of all pancreatic neoplastic disease. Although the majority of these tumors are sporadic (90 %), pNETs can arise in the setting of several different hereditary genetic syndromes, most commonly multiple endocrine neoplasia type 1 (MEN1). The presentation of pNETs varies widely, with over 60 % having malignant distant disease at the time of initial diagnosis involving the liver or other distant sites. Functioning pNETs represent approximately 10 % of all pNETs, secrete a variety of peptide hormones, and are responsible for several clinical syndromes caused by profound hormonal derangement. Surgery remains the cornerstone of therapy and the only curative approach. It should be pursued for localized disease and for metastatic lesions amenable to resection. Multimodality therapies, including liver-directed therapies and medical therapy, are gaining increasing favor in the treatment of advanced pNETs. Their utility is multifold and spans from ameliorating symptoms of hormonal excess (functional pNETs) to controlling the local and systemic disease burden (non-functional pNETs). The recent introduction of target molecular therapy has promising results especially for the treatment of progressive well-differentiated G1/G2 tumor. In this review, we summarize the current knowledge and give an update on recent advancements made in the therapeutic strategies for pNETs.

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Section: Somatostatin Analogues and Peptide Receptor Radiotherapysupporting

confidence: 87%

Pancreatic Neuroendocrine Tumors: an Update

2015

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“…Non-invasive determination of intratumoral heterogeneity as assessed by baseline somatostatin receptor (SSTR)-positron emission tomography (PET) before PRRT has already proven its prognostic performance by outperforming conventional PET parameters, such as mean/maximum standardized uptake values (SUV mean/ max ) in a mixed cohort of patients scheduled for endoradiotherapy [13]. However, in particular for pNET, PRRT efficacy prediction has not been elucidated yet due to considerable heterogeneous diversity, earlier relapse of pNET patients undergoing radionuclide therapy, or mechanisms of tumor escape in dedifferentiated tumors [14][15][16]. Decoding a general prognostic phenotype [10], we hypothesized that intratumoral textural feature (TF) analysis assessed by a baseline SSTR-PET might address the urgent clinical need of prognostication in G1/2 pNET patients prior to PRRT.…”

Section: Introductionmentioning

confidence: 99%

Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy

et al. 2018

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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.

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“…The evidence base for PRRT in metastatic pancreatic NETs is limited to numerous large consecutive series. Ezzidin et al analysed 68 patients with Grade 1 or 2 progressive advanced pancreatic NETs treated with 177 Lu-DOTATATE resulting in PFS of 34 months, with reversible Grade 3 or more haematotoxicity in 5.9% and no significant nephrotoxicity (Ezziddin et al 2014). A series of 52 patients with metastatic FDG avid (predominantly Grade 2) GEP NET from our institution treated with 177 Lu-DOTATATE combined with radiosensitising 5-fluorouracil chemotherapy demonstrated PFS of 48 months with negligible Grade 3 or 4 toxicities (Kashyap et al 2015).…”

Section: Peptide Receptor Radionuclide Therapymentioning

confidence: 99%

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

Pattison¹,

Hicks²

2017

Endocrine-Related Cancer

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There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors (somatostatin receptors (SSTRs) and glucagon-like peptide-1 receptor (GLP-1R)) the amine precursor uptake and decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[ 18 F]-l-fluoro-l-3,4-dihydroxyphenylalanine ( 18 F-FDOPA), and glycolytic metabolism with 2-[ 18 F]fluoro-2-deoxy-d-glucose (FDG). Accurate preoperative localisation and staging is critical to enable directed surgical excision or enucleation with minimal morbidity and preservation of residual pancreatic function. Benign insulinoma has near ubiquitous dense GLP-1R expression enabling accurate localisation with radiolabelled-exendin-4 compounds (e.g. 68 Ga-NOTA-exendin-4 PET/CT), whilst the rarer and more difficult to manage metastatic insulinoma typically express SSTR and is preferably imaged with radiolabelled-SSTR analogues such as 68 Ga-DOTA-octreotate (DOTATATE) PET/CT for staging and assessment of suitability for peptide receptor radionuclide therapy (PRRT). Similar to other metastatic neuroendocrine tumours, FDG PET/CT is used in the setting of highergrade metastatic insulinoma to provide important prognostic information that can guide treatment and determine suitability for PRRT. Interestingly, these three tracers appear to represent a spectrum of differentiation, which we conceptually describe as the 'tripleflop' phenomenon, with GLP-1R > SSTR > FDG in benign insulinoma and the opposite in higher-grade disease. This paper will review the clinical syndromes of adult hypoglycaemia (including a practical overview of the differential diagnoses to be considered), comparison of techniques for insulinoma localisation with emphasis on molecular imaging before discussing its implications for management of metastatic insulinoma.

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Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

Cited by 169 publications

References 43 publications

Pancreatic Neuroendocrine Tumors: an Update

Pancreatic Neuroendocrine Tumors: an Update

Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

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