Peptide Receptor Radionuclide Therapy with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland

Abstract

Aim: Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this treatment option still needs clinical evaluation. Methods: In this study, we evaluated the PRRT treatment response of 69 Danish patients with NET mainly originating from the gastroenteropancreatic system. Fifty-six patients (81%) were referred for PRRT to the Department of Nuclear Medicine, University Hospital Basel, Switzerland, between 2004 and 2008 due to progression assessed by the referring physicians. However, when retrospectively evaluated, only 42 of the 69 patients (61%) had progression according to RECIST (Response Evaluation Criteria in Solid Tumors). Most patients were treated with ⁹⁰Y-DOTATOC. Results: Based on RECIST, a complete response was observed in 5 patients (7.4%), a partial response in 11 patients (16.2%) and stable disease in 42 patients (61.8%). Progressive disease after completed therapy was observed in 10 patients (14.7%). The median progression-free survival was 29 months (95% CI: 22–36 months). Pancreatic NET seemed to respond better to PRRT than small intestinal carcinoid tumors (p = 0.03). The overall frequency of serious adverse events was low. Conclusion: Implementation of PRRT in clinical routine has provided a valuable new therapeutic option for the treatment of advanced NET. We suggest that PRRT may advance from second- or third-line to first- or second-line therapy in inoperable/unresectable NET patients.

64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients

“…Still, whether 10 or 15 liver metastases are found is not necessarily important additional information. However, also when analyzing organ by organ, 58 additional organ systems were found to be involved in 40 patients when 64 Cu-DOTATATE was used, compared with 111 In-DTPA-OC, which could potentially be of importance for the prognosis (23,24) and treatment selection (25)(26)(27)(28). Nevertheless, more foci found by PET are not necessarily representative of true-positive foci.…”

In vivo evaluation of PEGylated 64Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

“…FDG is mainly suitable for diagnosing tumors with high proliferative activity [1,6] and has limited diagnostic value for several cancer forms such as highly differentiated neuroendocrine (NE) [7,8] and prostatic tumors [9,10]. PET isotopes such as 18 F, 15 O, 13 N and 11 C have relative short half-lives where only early imaging time-points are possible, leaving biological processes with duration of several hours or days impossible to explore [11]. Tumor imaging using the longer lived PET isotope 64 Cu, with favorable decay characteristics (12.7 h), permit studies for as long as 48 h after injection [12,13].…”

“…NE tumors are known to express specific tumor markers, and approximately 90% of NE tumors have somatostatin receptors over-expressed on tumor cell surfaces [14]. Accordingly, these patients are well suited for peptide receptor radionuclide therapy (PRRT), which has been used for approximately 10 years based on either 90 Y-DOTATOC or 177 Lu-DOTATATE [15][16][17]. The dose-limiting organs for PRRT are the kidney and bladder due to renal excretion of the peptide-based tracer, and tracers limiting this absorbed dose to normal organs are warranted.…”

Whither peptide receptor radionuclide therapy for neuroendocrine tumors: an Einsteinian view of the facts and myths

“…Severe, grade 3 or 4 hematological toxicity occurs in less than 15 % [26,27,37,38]. A highgrade potentially life-threatening bone marrow toxicity (myelodysplasia) is reported in up to 2 % [39][40][41]. An association with prior chemotherapy or radiotherapy has been implicated and may represent a confounding factor in assigning a causal relationship [31].…”

“…Some centers suggest a combination of both 90 Y-DOTATOC and 177 Lu-DOTATATE in sequence or as a cocktail to deal with small and large metastases synchronously [40]. Increase in radiosensitivity as a measure to increase the objective response rate has shown some promising results [46].…”