Treatment of high grade metastatic neuroendocrine tumor (mNET) with peptide receptor radionuclide therapy (PRRT): Retrospective analysis in a single referral center.

To date, limited data are available concerning peptide receptor radionuclide therapy (PRRT) of grade 3 (G3) neuroendocrine neoplasms (NENs) with a Ki-67 proliferation index of >20%. The purpose of this study was to analyze the long-term outcome, efficacy and safety of PRRT in patients with SSTR-expressing G3 NEN. A total of 69 patients (M=41 males; age 28-81 years) received PRRT with lutetium-177 (Lu) and/or yttium-90 (Y) labeled somatostatin analogs (DOTATATE or DOTATOC). Twenty-two patients had radiosensitising chemotherapy. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS), defined from start of PRRT, including a subgroup analysis for patients with a Ki-67 of ≤55% and >55%. Treatment response was evaluated according to RECIST 1.1 as well as by molecular imaging criteria (EORTC). Short and long-term toxicity was documented (CTCAE v.5.0) using a structured database (comprising over 250 items per patient) and retrospectively analyzed. Forty-six patients had pancreatic, 11 CUP, 6 midgut, 3gastric, and 3 rectal NEN. Median follow-up was 94.3 months. The median PFS was 9.6 months and median OS was 19.9 months. For G3 NEN with a Ki-67 ≤55% ( = 53), the median PFS was 11 months and median OS 22 months. Patients with a Ki-67 >55% ( = 11), had a median PFS of 4 months and a median OS of 7 months. For those patients with positive SSTR imaging, but no FDG uptake, the median PFS was 24 months and median OS was 42 months. A significant difference was found for both, PFS and OS, with a median PFS of 16 vs 5 months and a median OS of 27 vs 9 months for a SUV >15.0 and a SUV ≤15.0 on SSTR-PET, respectively. In the group with FDG scored as 3-4, the median PFS was 7.1 months and the median OS 17.2 months. For FDG scored as 0-2, the median PFS was 24.3 months and the median OS 41.6 months. PRRT was well-tolerated by all patients; no grade 3 or grade 4 hematotoxicity occurred and no clinically significant decline in renal function was observed. There was no hepatotoxicity. PRRT was tolerated well without significant adverse effects and is efficacious in G3 NEN with promising clinical outcome, especially in patients with a Ki-67 index of ≤55% and even in patients who have failed chemotherapy. Baseline FDG along with SSTR molecular imaging is useful to stratify those G3-NEN patients with high uptake on SSTR PET/CT and no or minor FDG-avidity, a mismatch pattern which is associated with a better long term prognosis.

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“…6 and 7). Only a few PRRT studies have included patients with G3 NENs or NENs with a high proliferation index (5,(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety and Survival Analysis in 69 Patients

et al. 2018

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“…These 3 studies also seemed to have a higher median cumulative dose of 177 Lu than those reported by the other studies included in Figure 2. There is unfortunately no full data reported in the study by Armaghany et al (32), as it is only a presented abstract. The studies by Thapa et al (33), Ezziddin et al (34), and Yalchin et al (35) are larger studies focused mainly on low-grade disease and included only 5, 7, and 2 patients, respectively, with a Ki-67 of more than 20%, thus making it difficult to draw any conclusions.…”

Section: Therapeuticsmentioning

confidence: 98%

“…Six of the 13 studies included in Tables 4-6 do not include outcomes of the G3 patients, and only 4 commented on the degree of differentiation. Of the 7 (7/13) studies (29)(30)(31)(32)(33)(34)(35) that directly measured the outcome of the G3 patients, there were a total of 151 patients in whom imaging studies could be tracked over time after receiving PRRT. Of these 151 patients, 99 (66%) demonstrated either stable disease, partial response, or complete response.…”

Section: Therapeuticsmentioning

confidence: 99%

Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

2019

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The diagnosis and subsequent therapy of neuroendocrine neoplasms (NENs) have long relied on somatostatin receptor (SSTR) expression. The field of theranostics now uses newer SSTR-based PET imaging with 68 Ga-DOTATATE or 68 Ga-DOTATOC as a prerequisite for the administration of peptide receptor radionuclide therapy (PRRT). In the United States, Food and Drug Administration approval of 177 Lu-DOTATATE, a form of PRRT, in 2018 for use in gastroenteropancreatic NENs was obtained on the basis of prolonged progression-free survival versus high-dose octreotide longacting release in a phase III clinical trial of well-differentiated midgut NENs. Well-differentiated grade 1 and grade 2 NENs have a low proliferation index (Ki-67 , 20%) and longer overall survival (.10 y), whereas higher-grade (grade 3 [G3]) NENs have a high Ki-67 (.20%) and shorter overall survival (,1 y). Here, we present a review on the role of SSTR-based imaging and PRRT in G3 NENs, including a discussion of well-differentiated G3 NENs, the newest histologic classification. Some studies suggest that G3 NENs are less likely to be positive on SSTR-based imaging (but more likely on 18 F-FDG PET) than are well-differentiated NENs, but these data are limited. We found only 13 studies mentioning the use of PRRT in G3 NENs and a total of only 151 patients across these studies in whom radiologic response was measured. Of these 151 patients, 99 (66%) demonstrated at least stable disease or a partial response, indicating that some G3 NENs can be responsive to PRRT. We suggest that patients with G3 NENs should receive both 18 F-FDG PET and SSTR-based imaging to aid in both diagnosis and treatment selection, as positivity on SSTR-based imaging helps with patient identification for PRRT and discordance may suggest important clues to tumor biology and prognosis. However, prospective studies are needed to fully understand the role of PRRT in G3 NENs, especially in well-versus poorly differentiated G3 disease.

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Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) - a single-institution retrospective analysis

Thang

Lung

Kong

et al. 2017

Eur J Nucl Med Mol Imaging

111

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Treatment of high grade metastatic neuroendocrine tumor (mNET) with peptide receptor radionuclide therapy (PRRT): Retrospective analysis in a single referral center.

Cited by 5 publications

References 0 publications

Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety and Survival Analysis in 69 Patients

Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety and Survival Analysis in 69 Patients

Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) - a single-institution retrospective analysis

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