scholarly journals The next generation of peptide receptor radionuclide therapy

2019 ◽  
Vol 26 (8) ◽  
pp. C7-C11 ◽  
Author(s):  
Tessa Brabander ◽  
Julie Nonnekens ◽  
Johannes Hofland
Keyword(s):  
Radionuclide Therapy ◽  
Radiation Effects ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Heat Shock Protein 90 ◽  
Neuroendocrine Neoplasms ◽  
New Developments ◽  
Peptide Receptor ◽  
Promising Target ◽  
New Findings

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-[Tyr3]octreotate has been successfully developed in the last decades for the treatment of neuroendocrine neoplasms. However, different methods to improve the objective response rate and survival are under investigation. This includes changes of the radioligand, dosimetry and combination therapy with different agents, such as radiosensitisers. Hofving et al. recently reported, in the April 2019 issue of Endocrine-Related Cancer, the use of heat-shock protein 90 (Hsp90) modulation to augment radiation effects as a new promising target for radiosensitisation. In this commentary, new developments in the field of PRRT are discussed, placing these new findings about Hsp90 inhibitors into context.

scholarly journals Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy

2019 ◽  
Vol 43 (2) ◽  
pp. 246-253 ◽  
Author(s):  
A. J. A. T. Braat ◽  
H. Ahmadzadehfar ◽  
S. C. Kappadath ◽  
C. L. Stothers ◽  
A. Frilling ◽  
...  
Keyword(s):  
Liver Disease ◽  
Clinical Response ◽  
Radionuclide Therapy ◽  
Objective Response ◽  
Case Series ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Entire Study ◽  
Peptide Receptor ◽  
Resin Microspheres

Abstract Purpose Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT. Methods Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected. Results Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3–4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8–5.1 years] after radioembolization for the entire study population was found. Conclusion Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare. Level of Evidence 4, case series.

Intra-Arterial Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumor Liver Metastases

2019 ◽  
Vol 03 (01) ◽  
pp. 081-090 ◽  
Author(s):  
Sander Ebbers ◽  
Maarten Barentsz ◽  
Arthur Braat ◽  
Marnix Lam
Keyword(s):  
Liver Metastases ◽  
Radionuclide Therapy ◽  
Liver Tumors ◽  
Objective Response ◽  
Hepatic Metastases ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Original Research ◽  
Treatment Schedule ◽  
Peptide Receptor

Purpose Currently, peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-DOTATATE is used in patients with progressive neuroendocrine neoplasms (NEN) as salvage therapy. The standard treatment schedule consists of multiple cycles of intravenous (IV) administration. However, patients with liver metastases suffer from reduced tumor targeting and worse response and survival. This review provides an overview of the available evidence on the intra-arterial (IA) administration of radionuclide-labeled somatostatin analogues. Methods Databases of PubMed and Embase were searched systematically in May 2018 for studies that addressed IA PRRT. Included studies were original research publications focusing on absorbed tumor dose or tumor response after IA administration of PRRT for NEN. Publications on combined PRRT with other therapies or treatment of nonhepatic sites were excluded. Included publications were critically appraised on quality and their results reported accordingly. Results Seven publications were included in this review, including a total of 114 patients treated IA with different types of radiopeptides. Objective response was seen in 13 to 69% of the patients and disease stabilization in 18 to 52%. Disease progression occurred in 0 to 29% of the patients. IA administration resulted in a 1.06 to 9.2-fold increase in tumor-to-nontumor dose ratios in liver tumors, while normal liver and kidney doses remained within expected ranges. The incidence of adverse events was comparable to IV administration. Conclusion There is limited evidence that IA application of PRRT results in higher tumor-to-non-tumor dose ratios compared with IV infusion. IA administration of 177Lu-DOTATATE seems to be a promising new improvement in current clinical practice, achieving a higher absorbed tumor dose in patients with hepatic metastases of NEN.

Effectiveness of peptide receptor radionuclide therapy for neuroendocrine neoplasms: A multi-institutional registry study with prospective follow-up.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4033-4033
Author(s):  
Dieter Hörsch ◽  
Keyword(s):  
Small Bowel ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
Neuroendocrine Neoplasms ◽  
Registry Study ◽  
Free Survival ◽  
Peptide Receptor ◽  
Well Differentiated

4033 Background: Peptide receptor radionuclide therapy targets somatostatin receptors expressed on well differentiated neuroendocrine neoplasms. Retrospective monocentric studies indicate that peptide receptor radionuclide therapy is an effective treatment for patients with neuroendocrine neoplasms. Methods: We initiated a multi-institutional, prospective and board reviewed registry study for patients treated with peptide receptor radionuclide therapy. 450 patients were included and followed for a mean of 24.4 months. Patients were treated with Lutetium-177 (54%), Yttrium-90 (17%) or both radionuclides (29%). Primary neuroendocrine neoplasms were derived of pancreas (38%), small bowel 30%), unknown primary (19%), lung (4%) and colorectum (3,5%). Most neuroendocrine neoplasms were well differentiated with a proliferation rate below 20% in 54% and were pretreated by 1 or more therapies in 73%. Results: Overall survival of all patients from the beginning of therapy was 59 months in median. Median survival depended on radionuclides used (Yttrium-90: 38 months; Lutetium-177: not reached; both: 58 months), proliferation rate (G1: median not reached; G2: 58 months; G3: 33 months; unknown: 55 months) and origin of primary tumors (pancreas: 53 months; small bowel: not reached; unknown primary: 47 months; lung: 38 months) but not upon number of previous therapies. Median progression-free survival measured from last cycle of therapy accounted to 41 months for all patients. Progression-free survival of pancreatic neuroendocrine neoplasms was 39 months in median. Similar results were obtained for neuroendocrine neoplasms of unknown primary with a median of 38 months whereas neuroendocrine neoplasm of small bowel were progression-free for a median of 51 months. Side effects like G3-G4 nephrotoxicity or hematological function were observed in 0.2% and 2% of patients. Conclusions: Peptide receptor radionuclide therapy is effective for patients with G1-G2 neuroendocrine tumors irrespective of previous therapies with a survival advantage of several years compared to other therapies and only minor side effects.

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