Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms

Baüm, Richard; Kulkarni, Harshad; Singh, Aviral; Kaemmerer, Daniel; Müeller, Dirk; Prasad, Vikas; Hommann, Merten; Robiller, F; Niepsch, Karin; Franz, Holger; Jochems, Arthur; Lambin, Philippe; Hörsch, Dieter

doi:10.18632/oncotarget.24524

Cited by 122 publications

(144 citation statements)

References 40 publications

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“…Multivisceral transplantation has been used in a very small number of cases [202,203]. Novel concepts include neoadjuvant PRRT [179,204,205], or adjuvant SSA therapy post-transplant to reduce the risk of recurrence.…”

Section: Surgical Management Of Nelmsmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeu-tic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.According to SEER version 18, SBNEN and PanNEN incidences are currently estimated at 1.2 and 0.7 per 100,000, respectively [5]. The overall 20-year duration prevalence of all NEN is estimated at 171,321; SBNEN constituting 32,122 patients with 3-fold fewer PanNEN (10,707) [5]. Possible attributable factors for this increase evolving epidemiology include increased use of endoscopy and also improvements in the sensitivity of widely used imaging modalities, leading to increased detection of early-stage, asymptomatic disease [5].The median overall survival (OS) for NEN (irrespective of site and grade) is 9.3 years [5]. For SB (median OS: 14 years), this ranges from 70 months (advanced disease with distant metastases) to 170 months (localised disease) and from 30 months (Grade 3) to 160 months (Grade 1). For pancreas (median OS: 3.6 years): 21 months (advanced) to 235 months (localised disease) and from 15 months (Grade 3) to 140 months (Grade 1) [5].Multivariable analyses have identified that ethnicity, age, differentiation, stage and site all have statistically significant correlations with survival. In general, Caucasian ethnicity, age (< 50 years) and localised, well-differentiated NEN exhibit the best survival. SB tumour patients are approximately 1.5 times more likely to survive longer than those with PanNEN [19]. Many of these correlations are self-evident since they pertain to degree of malignancy, disease duration and patient performance status.OS (median 5-year) app...

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Section: Surgical Management Of Nelmsmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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“…42 Patients who have high volume and symptomatic PanNETs with negative SSTR findings on scintigraphy may be treated with chemotherapy (capecitabine/temozolomide), 43 liver-directed intervention (embolization, chemoembolization, radioembolization, cytoreduction/ablation), 44,45 targeted agents, namely, everolimus and/or sunitinib, 38,46 or peptide receptor radionucleotide therapy with 177 Lu-DOTATATE. [47][48][49] Poorly differentiated PanNEC represents a biologically distinct entity from well-differentiated PanNET. Given the clinical presentation of advanced stage and rapid progression, most PanNECs are not amenable to surgical resection and require direct cytotoxic chemotherapy; platinum with etoposide is usually the first-line option.…”

Section: Molecular and Genomicsmentioning

confidence: 99%

Pancreatic Neuroendocrine Neoplasms: Landscape and Horizon

Tang

2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Since the initial description of pancreatic endocrine physiology and the recognition of islet cell tumors in the 1800s, there have been noteworthy advances in the pathobiology of pancreatic neuroendocrine neoplasms (PanNENs), and definition of the important distinction between well-differentiated neuroendocrine tumor (PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC). The evolving knowledge has resulted in a continuous update in terminology, classification, and grading system for this group of neoplasms. Pancreatic neuroendocrine tumors associated with hereditary conditions have been linked to unique molecular and genetic events, and sporadic PanNETs have specific gene signatures. Based on accumulative experience and knowledge, therapeutic strategies have been defined for this group of neoplasms. Objective.— To review the evolution and description of the pathologic-genomic evolution of PanNENs, and to facilitate accurate pathologic interpretation for the corresponding clinical management. Data Sources.— Literature review of published studies and author's own work. Conclusions.— Evolving experience and knowledge have established subtypes of pancreatic neuroendocrine neoplasms, based on their genotype and phenotype. Accurate pathologic interpretation of the specific neoplasm has significant implications for therapy and prognosis.

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“…For example, in the NETTER-1 trial, the inclusion criteria relied on interpretation of the 111 In-pentetreotide scintigraphy results using the Krenning score (eligible if the highest lesion uptake equaled or exceeded liver uptake) (8). European centers have used both 111 In-pentetreotide scintigraphy and SSTR PET for patient selection (9,10). The common approach for characterizing uptake on SSTR PET is to use a modified Krenning score in which the same qualitative approach (comparison to liver uptake) is applied to SSTR PET (6,11).…”

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confidence: 99%

¹¹¹In-Pentetreotide Scintigraphy Versus ⁶⁸Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden

et al. 2019

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Eligibility for somatostatin receptor (SSTR) radionuclide therapy uses the qualitative Krenning score based on 111 In-pentetreotide planar scintigraphy as was performed in the NETTER-1 trial. The purpose of this study was to determine the effect of using SSTR PET-based Krenning score in comparison to 111 In-pentetreotide. Methods: This was a post hoc headto-head comparison of 68 Ga-DOTATATE-based and 111 In-pentetreotide-based Krenning scores in 150 patients included in a prospective phase 2 study (NCT01967537). Patients were imaged using 68 Ga-DOTA-TATE PET/CT, 111 In-pentetreotide planar scintigraphy, and SPECT/CT within 1 wk. SSTR ligand uptake was graded using the Krenning score independently by 3 readers. Results: The detection rate of SSTRexpressing disease (Krenning scores 2-4) was 23%, 38%, and 72% with planar imaging, SPECT, and SSTR PET, respectively. The Krenning score was higher with SSTR PET (2.71 ± 1.74) than with planar imaging (0.75 ± 1.37; P , 0.001) or SPECT (1.23 ± 1.57; P , 0.001). In patients with a Krenning score of at least 3 on SSTR PET, the detection rate of planar imaging and SPECT was lower for lesions smaller than 2 cm than lesions 2 cm or larger: 15% and 24% versus 78% and 89%, respectively (P , 0.001). For lesions larger than 5 cm, Krenning scores between SSTR PET and 111 In-pentetreotide were nearly equivalent. Lesion size did not have an impact on SSTR PET Krenning scores. Interreader agreement was higher for SSTR PET than for planar imaging or SPECT (0.79 vs. 0.67 and 0.50, respectively). Conclusion: SSTR PET results in higher Krenning scores than 111 In-pentetreotide, particularly when lesions measured 2 cm or less. Small lesion size resulted in low Krenning scores using 111 In-pentetreotide, but lesion size did not affect SSTR PET-based Krenning scores. The results of the NETTER-1 trial cannot be directly applied to patients with small lesions. Further study of peptide receptor radionuclide therapy in patients with small lesions negative on 111 In-pentetreotide imaging and positive on SSTR PET is warranted.

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Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms

Cited by 122 publications

References 40 publications

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Pancreatic Neuroendocrine Neoplasms: Landscape and Horizon

¹¹¹In-Pentetreotide Scintigraphy Versus ⁶⁸Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden

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Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms

Cited by 122 publications

References 40 publications

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Pancreatic Neuroendocrine Neoplasms: Landscape and Horizon

111In-Pentetreotide Scintigraphy Versus 68Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden

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¹¹¹In-Pentetreotide Scintigraphy Versus ⁶⁸Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden