Specific efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced neuroendocrine tumours of the small intestine
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Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with 177Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort.
A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1–2 stage IV treated with 177Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements.
The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25–41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were functionality [hazard ratio (HR) 2.1, 95 % CI 1.0–4.5, p = 0.05] and high plasma chromogranin A (CgA) levels > 600 ng/ml (HR 2.9, 95 % CI 1.5–5.5, p < 0.001) at baseline.
PRRT is well tolerated and very effective in advanced well-differentiated small intestinal (midgut) NET. A high disease control rate and long PFS can be achieved with this modality after failure of standard biotherapy with somatostatin analogues. Tumour functionality and high plasma CgA appear to be independent predictors of unfavourable patient outcome.
KeywordsPRRT Radiopeptide therapy NET Neuroendocrine tumors Small bowel NET Midgut NET Functional NET Small intestinal NET Somatostatin Receptor targeted radionuclide therapy
Compliance with ethical standards
Conflicts of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
Informed consent was obtained from all individual participants included in the study.
Source of funding
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
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