Safety and Efficacy of Peptide-Receptor Radionuclide Therapy in Elderly Neuroendocrine Tumor Patients

Peptide receptor radionuclide therapy (PRRT) is a well-established treatment in somatostatin receptor-expressing neuroendocrine tumours (NETs). The safety and efficacy of PRRT in >79 years old patients (EP) have not been systematically investigated. All patients with inoperable/metastatic/progressive G1/G2 NET, >79 years (EP), treated with PRRT at the University Hospital of Basel between 2006 and 2018, were enrolled in this retrospective matched cohort study. Each patient was manually matched with ≥1 younger patient (YP = 60–70 years). The primary endpoint was toxicity. Toxicity (subacute, long-term) was graded according to the criteria for adverse events (CTCAE) v5.0. All toxicity grades ≥ 3, or whose delta (Δ) to baseline were ≥2, were considered significant. The odds ratio (OR) for developing toxicity was tested for non-inferiority of EP vs. YP. Clinical response to PRRT and overall survival (OS) were assessed as secondary outcome measures. Forty-eight EP and 68 YP were enrolled. Both cohorts were balanced regarding median time since diagnosis, tumour location, grading, treatment scheme, and baseline biochemical parameters, except for eGFR (EP: 61 ± 16 vs. YP: 78 ± 19; mL/min/1.73 m2). Twenty-two grade ≥ 3 or Δ ≥ 2 subacute hematotoxicities occurred in 10 EP (10.3% of cycles) and 37 in 19 YP (11.6% of cycles; p = NS). Long-term grade ≥ 3 renal toxicity occurred in 7 EP and 2 YP (p = NS). The median OS was 3.4 years (EP) vs. 6.0 years (YP), HR: 1.50 [0.75, 2.98], p = NS. PRRT is a valid therapeutic option in elderly NET patients with similar toxicity and non-inferior survival compared to matched younger patients.

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Haematotoxicity during peptide receptor radionuclide therapy: Baseline parameters differences and effect on patient’s therapy course

PLoS ONE ◽

10.1371/journal.pone.0260073 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0260073

Author(s):

Daphne M. V. de Vries–Huizing ◽

Michelle W. J. Versleijen ◽

Michiel Sinaasappel ◽

Iris Walraven ◽

Martine M. Geluk–Jonker ◽

...

Keyword(s):

Radionuclide Therapy ◽

Selection Criteria ◽

Progressive Disease ◽

Neuroendocrine Tumour ◽

Somatostatin Receptor ◽

Peptide Receptor Radionuclide Therapy ◽

Tumour Volume ◽

Clinical Impact ◽

Peptide Receptor ◽

Grade 3

Background Mainly severe (CTCAE grade 3–4) haematotoxicity during peptide receptor radionuclide therapy (PRRT) is reported in literature due to major clinical impact, however moderate (CTCAE grade 2) haematotoxicity is common and could affect therapy management. The aim of this study was to evaluate the haematotoxicity course during PRRT and to compare baseline parameters between haematotoxicity grades. Methods In this retrospective study, 100 patients with a neuroendocrine tumour treated with PRRT were included. Patients were treated with an aimed number of four cycles with 7.4 GBq [177Lu]Lu-DOTA-TATE administered every 10 weeks. Haematological assessment was performed at baseline and frequently up to 10 weeks after the fourth cycle. The lowest haematological value was graded according to CTCAE v5.0, and patients were classified using the highest observed grade. Differences in baseline parameters, including [68Ga]Ga-DOTA-TATE positive tumour volume, were evaluated between CTCAE grades. Results Four cycles were completed by 86/100 of patients, 4/100 patients discontinued due to haematotoxicity, and 10/100 patients due to progressive disease. The treatment course was adjusted due to haematotoxicity in 24/100 patients, including postponed next cycle (n = 17), reduced administered activity (n = 13), and both adjustments (n = 10). The most observed haematotoxicity grade was grade 0–1 in 54/100 patients, grade 2 in 38/100 and grade 3–4 in 8/100. Significant differences in baseline leucocyte, neutrophil and platelet counts were observed between grade 0–1 and grade 2. However, the correlation between baseline and lowest observed values was poor to moderate. No differences between haematotoxicity grades and baseline parameters or somatostatin receptor positive tumour volume was observed. Conclusions The incidence of severe haematotoxicity was low with extensive screening and monitoring. The vast majority of patients (96/100) was not restricted in treatment continuation by haematotoxicity; therefore, our selection criteria appeared appropriate for safe PRRT treatment. Baseline parameters showed limited correlation with the degree of decline in haematological values.

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Safety and efficacy of sequential local ablative therapy and peptide receptor radionuclide therapy in patients with neuroendocrine neoplasms and high tumor load; An analysis of 50 sequential patients

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0035-1547651 ◽

2015 ◽

Vol 122 (03) ◽

Author(s):

D Hörsch

Keyword(s):

Radionuclide Therapy ◽

Peptide Receptor Radionuclide Therapy ◽

Neuroendocrine Neoplasms ◽

Safety And Efficacy ◽

Ablative Therapy ◽

Peptide Receptor ◽

Local Ablative Therapy ◽

Tumor Load

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Intraindividual comparison of [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05177-z ◽

2021 ◽

Author(s):

Heribert Hänscheid ◽

Philipp E. Hartrampf ◽

Andreas Schirbel ◽

Andreas K. Buck ◽

Constantin Lapa

Keyword(s):

Radionuclide Therapy ◽

Therapeutic Agent ◽

Somatostatin Receptor ◽

Absorbed Dose ◽

Peptide Receptor Radionuclide Therapy ◽

Somatostatin Analogue ◽

Target Tissue ◽

Peptide Receptor ◽

Intraindividual Comparison ◽

Administered Activity

Abstract Purpose The radiolabelled somatostatin analogue [177Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [177Lu]Lu-DOTA-TOC. Methods Activity kinetics in organs and tumours after [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy. Results In comparison to [177Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [177Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [177Lu]Lu-DOTA-TOC in 4 of 5 patients. Conclusions Prior to a treatment with [177Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.

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Predictive and Prognostic Impact of Blood-Based Inflammatory Biomarkers in Patients with Gastroenteropancreatic Neuroendocrine Tumors Commencing Peptide Receptor Radionuclide Therapy

Diagnostics ◽

10.3390/diagnostics11030504 ◽

2021 ◽

Vol 11 (3) ◽

pp. 504

Author(s):

Fiona Ohlendorf ◽

Rudolf Werner ◽

Christoph Henkenberens ◽

Tobias Ross ◽

Hans Christiansen ◽

...

Keyword(s):

Treatment Response ◽

Neuroendocrine Tumors ◽

Radionuclide Therapy ◽

Somatostatin Receptor ◽

Peptide Receptor Radionuclide Therapy ◽

Tumor Burden ◽

Inflammatory Biomarkers ◽

Whole Body ◽

Prognostic Impact ◽

Peptide Receptor

Tumor microenvironment inflammation contributes to the proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response. We aimed to evaluate the early predictive and prognostic significance of markers of systemic inflammation in patients receiving somatostatin-receptor targeted peptide receptor radionuclide therapy (PRRT). This retrospective observational cohort study included 33 patients with advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) treated with PRRT. Pretreatment blood-based inflammatory biomarkers, e.g., Creactive protein levels (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC), were documented and inflammation indexes, e.g., neutrophil-lymphocyte ratio (NLR) and Platelet × CRP multiplier (PCM), were calculated. Tumor burden was determined using [68Ga]GaDOTATATE PET/CT before enrollment and every 2 cycles thereafter until progression. Therapy response was assessed using RECIST 1.1, including its volumetric modification. Inflammatory biomarkers and inflammatory indexes demonstrated marked heterogeneity among patients, and were significantly higher in non-responders (e.g., CRP (P < 0.001), ANC (P = 0.002), and PCM (P < 0.001)). Change in whole-body tumor burden after two cycles of PRRT was significantly associated with CRP (P = 0.0157) and NLR (P = 0.0040) in multivariate regression analysis. A cut-off of 2.5 mg/L for CRP (AUC = 0.84, P = 0.001) revealed a significant outcome difference between patients with adversely high vs. low CRP (median PFS 508 days vs. not yet reached (HR = 4.52; 95% CI, 1.27 to 16.18; P = 0.02)). Tumor-driven systemic inflammatory networks may be associated with treatment response, change in tumor burden, and prognosis in patients with GEPNETs receiving PRRT.

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Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Patients With Somatostatin Receptor–Expressing Neuroendocrine Tumors

Pancreas ◽

10.1097/mpa.0000000000000113 ◽

2014 ◽

Vol 43 (4) ◽

pp. 518-525 ◽

Cited By ~ 70

Author(s):

Ebrahim S. Delpassand ◽

Amin Samarghandi ◽

Sara Zamanian ◽

Edward M. Wolin ◽

Mohammadali Hamiditabar ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Radionuclide Therapy ◽

Somatostatin Receptor ◽

Peptide Receptor Radionuclide Therapy ◽

Peptide Receptor

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Effect of Peptide Receptor Radionuclide Therapy on Somatostatin Receptor Status and Glucose Metabolism in Neuroendocrine Tumors: Intraindividual Comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT

International Journal of Molecular Imaging ◽

10.1155/2011/524130 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 18

Author(s):

Sowon Oh ◽

Vikas Prasad ◽

Dong Soo Lee ◽

R. P. Baum

Keyword(s):

Glucose Metabolism ◽

Neuroendocrine Tumors ◽

Fdg Pet ◽

Radionuclide Therapy ◽

Somatostatin Receptor ◽

Peptide Receptor Radionuclide Therapy ◽

Receptor Expression ◽

Peptide Receptor ◽

Pet Ct ◽

Fdg Pet Ct

The heterogeneous nature of the neuroendocrine tumors (NET) makes it challenging to find one uniformly applicable management protocol which is especially true for diagnosis. The discovery of the overexpression of somatostatin receptors (SMS-R) on neuroendocrine tumor cells lead to the generalized and rapid acceptance of radiolabeled somatostatin receptor analogs for staging and restaging of NET as well as for Peptide Receptor Radionuclide Therapy (PRRNT) using Y-90 and Lu-177 DOTATATE/DOTATOC. In this present work we tried to look in to the effect of PRRNT on the glucose metabolism assessed by F-18 FDG PET/CT and SMS-R density assessed by Ga-68 DOTANOC PET/CT. We observed a complex relationship between the somatostatin receptor expression and glucose metabolism with only 56% (77/138) of the lesions showing match, while the others show mismatch between the receptor status and metabolism. The match between receptor expression and glucose metabolism increases with the grade of NET. In grade 3 NET, there is a concurrence between the changes in glucose metabolism and somatostatin receptor expression. PRRNT was found to be more effective in lesions with higher receptor expression.

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RADIONUCLIDE IMAGING AND THERAPY OF NEUROENDOCRINE TUMOURS

Journal of Cancer & Allied Specialties ◽

10.37029/jcas.v1i2.30 ◽

2015 ◽

Vol 1 (2) ◽

Author(s):

Shaunak Navalkissoor ◽

Gopinath Gnanasegaran

Keyword(s):

Radionuclide Imaging ◽

Radionuclide Therapy ◽

Neuroendocrine Tumours ◽

Somatostatin Receptor ◽

Peptide Receptor Radionuclide Therapy ◽

Clinical Results ◽

It Use ◽

Peptide Receptor ◽

Mibg Therapy

The incidence and prevalence of neuroendocrine tumours (NETs) are on the rise. Although NETs are a heterogeneous group of tumours, they have some similar properties, for example, that they can concentrate neuroamines and tend to have a high degree of somatostatin receptor (SSR) expression. These mechanisms can be exploited and this article discusses the important role of radionculide imaging and radionculide therapy in the management of NETs based on these mechanisms. This article reviews the current literature and discusses the role of radionuclide imaging in NETs both in terms of SSR imaging and neuroamine (metaiodobenzylguanidine [MIBG]) imaging. We discuss state-of- the-art 68Ga-radiopeptide imaging and indications for it use. We also discuss the role of 18F-FDG and other tracers in the management of NETs. The second half of the article focuses on radiotargeted treatment of NETs, discussing I-131 MIBG therapy and focussing on the emergence of peptide receptor radionuclide therapy. We discuss the clinical results, toxicities and patient selection for PRRT. Key words: DOTA octreotide, DOTATATE, Ga-68, Lu-177, metaiodobenzylguanidine, neuroendocrine tumours, peptide receptor radionuclide therapy, Y-90

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Somatostatin receptor radionuclide therapy in neuroendocrine tumors

Endocrine Related Cancer ◽

10.1530/erc-20-0360 ◽

2021 ◽

Vol 28 (3) ◽

pp. R81-R93

Author(s):

Mintallah Haider ◽

Satya Das ◽

Taymeyah Al-Toubah ◽

Eleonora Pelle ◽

Ghassan El-Haddad ◽

...

Keyword(s):

Clinical Trials ◽

Radionuclide Therapy ◽

Somatostatin Receptor ◽

Somatostatin Analogs ◽

Peptide Receptor Radionuclide Therapy ◽

Study Data ◽

Combination Therapies ◽

Peptide Receptor ◽

Therapeutic Landscape ◽

Receptor Agonists And Antagonists

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic NETs. An understanding of benefits and risks is important for the appropriate implementation of this therapy. This review summarizes study data supporting the use of radiolabeled somatostatin analogs for the treatment of advanced NETs and highlights risks, including potential toxicities in specific populations. Key ongoing clinical trials, including randomized studies, are designed to better define the position of PRRT within the broader therapeutic landscape. Preclinical and early-phase human studies are focused on the development of novel somatostatin-receptor agonists and antagonists, new radionuclides, and radiosensitizing combination therapies.

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