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.

Single institution experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 623-623
Author(s):  
Heying Duan ◽  
Gaia Ninatti ◽  
Bradley Girod ◽  
Valentina Ferri ◽  
Pamela L. Kunz ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
Single Institution ◽  
Free Survival ◽  
Peptide Receptor ◽  
Low Toxicity

623 Background: Neuroendocrine tumors (NETs) are rare but increasing in incidence. The only curative treatment is surgery, which in many cases is not an option due to metastatic disease at diagnosis. The NETTER-1 study showed high efficacy and low toxicity of peptide receptor radionuclide therapy (PRRT) for midgut NETs. Here, we present our initial experience with PRRT in the treatment of patients with NET. Methods: Fifty-two patients (27 males and 25 females; 37 - 81 yo, mean ± SD: 61.8 ± 10.6 years) with documented progressive NET (25 pancreas, 17 small intestine, 1 coecum, 4 unknown primary, 3 paragangliomas, and 2 pheochromocytomas) were referred to undergo PRRT at our institution from July 2018 to September 2019. Laboratory tests were obtained at baseline, 1 week before each cycle and every 3 months following treatment. Progression-free survival (PFS), objective response rate (ORR) and toxicity were assessed. An interim overall survival (OS) analysis was performed. Results, when possible, were compared with the NETTER-1 trial. Lines of therapy were documented. Results: 22/52 (42%) patients completed all 4 cycles of PRRT. 18/52 (34%) patients are currently being treated. 12/52 (23%) patients had to discontinue treatment. Hematotoxicity was the only side effect which can be related to PRRT. The 6-month and 9-month PFS rate was 82.4% and 66.8% respectively vs. 89% and 84% in the NETTER-1 trial. The ORR was 36% vs. 18% in the NETTER-1 trial. In the interim OS analysis, 6 deaths occurred. In contrast to the NETTER-1 study, PRRT in our patient cohort was performed later in the course of treatment (median lines of therapy before PRRT = 4 ±1.3 (range 1-6)). Conclusions: Our preliminary data show overall good results of PRRT in patients with NETs. However, compared to the NETTER-1 trial, PFS is shorter which is most likely due to the extensive pretreatment, but ORR was higher. [Table: see text]

scholarly journals Effect of hormone secretory syndromes on neuroendocrine tumor prognosis

2017 ◽  
pp. R261-R274 ◽  
Author(s):  
Wouter T Zandee ◽  
Kimberly Kamp ◽  
Roxanne C van Adrichem ◽  
Richard A Feelders ◽  
Wouter W de Herder
Keyword(s):  
Radionuclide Therapy ◽  
Hormone Secretion ◽  
Somatostatin Analogs ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Peptide Receptor ◽  
Clinical Syndromes ◽  
Well Differentiated ◽  
Positive Effect

The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones. This has been reduced with several drugs: proton-pump inhibitors decrease acid secretion caused by gastrinomas. Somatostatin analogs can inhibit the secretion of multiple hormones and these are now the cornerstone for treating patients with a gastroenteropancreatic NET. However, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs and everolimus can also decrease symptoms of hypersecretion and increase progression-free survival. Several factors affect the survival in patients with a functioning NET. Complications of hypersecretion negatively impact survival; however, secretion of hormones is also often a sign of a well-differentiated NET and due to the symptoms, functioning NETs can be detected in an earlier stage suggesting a positive effect on prognosis. The effect on survival is also dependent on the type of hormone being secreted. This review aims to study the effect of hormone secretion on the prognosis of NETs with the contemporary treatments options available today.

scholarly journals 90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1463
Author(s):  
Licia Uccelli ◽  
Alessandra Boschi ◽  
Corrado Cittanti ◽  
Petra Martini ◽  
Stefano Panareo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Preclinical Studies ◽  
Peptide Fragment ◽  
Free Survival ◽  
Peptide Receptor ◽  
Yttrium 90

The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with β-emitting radionuclides, such as yttrium-90 and lutetium-177. In this review, covering twenty five years of literature, we describe the characteristics and performances of the two most used therapeutic radiopharmaceuticals for the NETs radio-treatment: [90Y]Y-DOTATOC and [177Lu]Lu-DOTATOC taking this opportunity to retrace the most significant results that have determined their success, promoting them from preclinical studies to application in humans.

Severe metabolic acidosis and hyperkalemia after peptide receptor radionuclide therapy. A case report, review of the literature and proposed treatment algorithm

2021 ◽  
pp. 239936932110197
Author(s):  
Nikolaos A Trikalinos ◽  
Hyun Kim ◽  
Amir Iravani ◽  
Lauren Henke ◽  
Anitha Vijayan
Keyword(s):  
Radionuclide Therapy ◽  
Treatment Algorithm ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Review Of The Literature ◽  
Peptide Receptor ◽  
Life Threatening ◽  
Well Differentiated ◽  
Intravenous Sodium ◽  
Electrolyte Abnormalities

Peptide receptor radionuclide therapy (PRRT) has been increasingly used in the treatment of patients with well-differentiated neuroendocrine neoplasms (WD-NENs), but electrolyte abnormalities during prophylactic aminoacid (AA) infusion can complicate its administration. We describe a case of AA-induced acidosis and hyperkalemia associated with PRRT. We tailored an oral and intravenous sodium bicarbonate regimen for pre-emptive treatment prior to subsequent PRRT session, thereby preventing hospitalization. We provide a relevant review of the literature and our treatment algorithm, that can serve as a point of reference in treatment of this life-threatening complication of PRRT.

scholarly journals A Clinical Efficacy of PRRT in Patients with Advanced, Nonresectable, Paraganglioma-Pheochromocytoma, Related to SDHx Gene Mutation

2019 ◽  
Vol 8 (7) ◽  
pp. 952 ◽  
Author(s):  
Kolasinska-Ćwikła ◽  
Pęczkowska ◽  
Ćwikła ◽  
Michałowska ◽  
Pałucki ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Radionuclide Therapy ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Open Label ◽  
Free Survival ◽  
Peptide Receptor ◽  
Radiological Response

Paragangliomas and pheochromytomas (PPGLs) exhibit variable malignancy, advanced/hormonally active/progressive need therapy. PRRT (Peptide Receptor Radionuclide Therapy) could be an option for these patients. To evaluate the effectiveness of PRRT (90Y DOTATATE), based on overall survival (OS) and progression-free survival (PFS), in patients with PPGLs, related to SDHx gene mutation, we conducted a prospective open-label, single-center, phase II study. Thirteen patients were observed, eight PGL1 and five PGL4, all with advanced, non-resectable tumors, and eight had metastases. All were treated with 90Y DOTATATE. Efficacy was based on OS and PFS, and radiological response was based on RECIST. Hormonal activity was evaluated using serum-fractionated free catecholamines. Eight subjects had a clinical response, three were stable, and two exhibited disease progression. Among four patients with hormonally-active PPGLs, three showed a reduction and one showed normalization. OS for all was 68.0 months; PFS was 35.0 months. OS in PGL4 = 25.0 vs. N.R. (not reached) in PGL1. PFS in PGL4 = 12.0 vs. N.R. in PGL1. A difference was seen in the OS and PFS in patients who did not respond clinically, compared to those who did, OS = 22.0 vs. N.R. PFS = 7.0 vs. N.R. A difference in the OS and PFS was noted in patients with liver and bone involvement compared to those without. PRRT is an effective therapy in selected population of patients with SDHx, in those with locally-advanced, non-resectable tumors. Furthermore, it is effective regardless of the secretory status.

scholarly journals Peptide receptor radionuclide therapy with 177Lu-DOTATATE for symptomatic control of refractory carcinoid syndrome

2021 ◽  
Author(s):  
Wouter T Zandee ◽  
Tessa Brabander ◽  
Anela Blažević ◽  
Noémie S Minczeles ◽  
Richard A Feelders ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Carcinoid Syndrome ◽  
Tertiary Care ◽  
Somatostatin Analogs ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Neuroendocrine Neoplasms ◽  
Care Hospital ◽  
Acid Excretion ◽  
Peptide Receptor

Abstract Context Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE results in an increase of progression-free survival and quality of life in patients with progressive well-differentiated neuroendocrine neoplasms (NENs). Objective To study the effect of 177Lu-DOTATATE in patients with carcinoid syndrome and radiologically stable or newly diagnosed disease treated solely for the purpose of symptom reduction. Design Retrospective cohort study Setting Tertiary care hospital Patients 22 patients with a metastatic midgut NEN, elevated urinary 5-hydroxyindolacetic acid excretion and flushing and/or diarrhea despite treatment with a somatostatin analog, without documented disease progression Intervention PRRT with 177Lu-DOTATATE (intended cumulative dose: 29.6 GBq) with a primary aim to reduce symptoms. Results After PRRT, mean bowel movement frequency (BMF) decreased from 6.1 ± 3.4 to 4.6 ± 3.6 per day (p=0.009). Flushes decreased from 4.3 ± 2.9 to 2.4 ± 2.7 flushes per day (p=0.002). A decrease of BMF of more than 30% occurred in 47% of patients with baseline BMF of 4 or more (n=17). In patients with ≥2 episodes of flushing a day (n=15), 67% of patients had more than 50% decrease of daily flushing. A decrease in urinary 5-hydroxyindolacetic acid excretion of more than 30% was seen in 56% of patients. The EORTC-C30 diarrhea subscale score showed a trend towards improvement by an average of 16.7 ± 33.3 points (p=0.11). Conclusion PRRT with 177Lu-DOTATATE effectively reduced diarrhea and flushing in patients with carcinoid syndrome and can be considered for symptomatic treatment of carcinoid syndrome insufficiently controlled with somatostatin analogs.

Surgery and peptide receptor radionuclide therapy: An effective multimodal approach for metastatic neuroendocrine tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4113-4113
Author(s):  
Andreja Frilling ◽  
Ashley Clift ◽  
Adil Al-Nahhas ◽  
Richard P. Baum ◽  
Daniel Kaemmerer
Keyword(s):  
Overall Survival ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Initial Diagnosis ◽  
Surgical Morbidity ◽  
Naive Patient ◽  
Free Survival ◽  
Peptide Receptor

4113 Background: Neuroendocrine neoplasia (NEN) of the pancreas (PanNEN) or small bowel (SBNEN) frequently present with metastases at initial diagnosis, undermining the efficacy of surgical treatment. Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues, 90Y-DOTATOC and 177Lu-DOTATATE, has been shown to achieve prolonged progression-free survival (PFS) and overall survival (OS) in a substantial number of non-surgical patients with advanced NEN. Our aim was to prospectively determine the efficacy of a combination of radical loco-regional surgery and 177Lu PRRT in patients with metastasised NEN. Methods: A set of inclusion criteria was defined (e.g. PanNEN or SBNEN, G1/G2 NEN, initial tumour diagnosis, treatment naïve patient, stage IV NEN, positivity on 68Ga DOTATATE or DOTATOC PET/CT, eligibility for surgery and PRRT). Patients underwent PRRT within 3 months following surgery. Follow-up included biochemistry and imaging. Outcome measures included 1-, 3-, and 5-year OS and PFS from initial diagnosis. Results: Forty-one patients met eligibility criteria and were included. There were 26 males (63.4%) and median age at surgery was 58.8 years (range 32.1-78.3). All patients with SBNEN underwent right hemicolectomy, terminal ileal resection and mesenteric lympadenectomy. In PanNEN patients either Whipple procedure or distal pancreatectomy and peripancreatic lymphadenectomy were performed. The median number of PRRT cycles was 4 (range 2-6). Post-treatment mortality was 0%. Surgical morbidity was 12% (all grade 1 according Clavien-Dindo) and transient grade 1 toxicity occurred post PRRT in 40%. There was no grade 3 toxicity. Median follow-up was 5.48 years (range 0.53 – 11.98). Median PFS and OS were 3.33 years and 9.07 years, respectively. Progression-free survival (with 95% CI) was at 1-, 3-, and 5-years 80% (68.7-92.6), 60.9% (45.9-75.9) and 43.3% (27.4-59.3), respectively. Overall survival (with 95% CI) at 1-, 3-, and 5-years was 97.6% (93-100), 97.6% (93-100), and 95% (87-100), respectively. Conclusions: Radical loco-regional surgery for primary tumours combined with PRRT provides a novel, highly efficacious approach in metastasised NEN.

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