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. 2025 Aug;52(10):3672-3681.
doi: 10.1007/s00259-025-07235-w. Epub 2025 Mar 26.

Safety and efficacy of re-treatment with [177Lu]Lu-DOTA-Octreotate radionuclide therapy in progressive gastro-entero-pancreatic neuroendocrine tumours - a single centre experience

Raghava Kashyap  1   2   3 , Ramin Alipour  4   5 , Emma Boehm  4   6 , Kerry Jewell  4   5 , Aravind S RaviKumar  4   5 , Anthony Cardin  4 , Javad Saghebi  4 , Michael S Hofman  4   5 , Michael T Fahey  5   7 , Michael Michael  5   8 , Tim Akhurst  4 , Rodney J Hicks  9   10   11 , Grace Kong  4   5
Affiliations

Safety and efficacy of re-treatment with [177Lu]Lu-DOTA-Octreotate radionuclide therapy in progressive gastro-entero-pancreatic neuroendocrine tumours - a single centre experience

Raghava Kashyap et al. Eur J Nucl Med Mol Imaging. 2025 Aug.

Abstract

Aim: Patients with gastro-entero-pancreatic neuroendocrine tumours (GEP NET) who retain somatostatin receptor (SSTR) expression after initial response to [177Lu]Lu-DOTA-Octreotate (LuTate) peptide receptor radionuclide therapy (PRRT) are amenable to re-treatment (R-PRRT) upon progression. We assessed the safety and efficacy of R-PRRT in patients with progressive metastatic GEP NET.

Materials and methods: A retrospective analysis, approved by institutional ethics board, was performed in patients with GEP NET who received R-PRRT for either symptomatically or radiologically progressive disease. Safety was assessed by renal and haematological parameters at 3 months post R-PRRT (CTCAE v5.0). Molecular imaging response was evaluated on [68Ga]Ga-DOTA-Octreotate (GaTate) PET/CT using pre-defined criteria. RECIST 1.1 responses 3 months post R-PRRT were documented when feasible. Progression-free and overall survival analysis were performed.

Results: A total of 63 patients had R1-PRRT (1-3 cycles). The majority (70%) had Grade 2 NET and small intestinal primary (51%). A second re-treatment course (R2-PRRT) was given in 20 patients and a third course (R3-PRRT) in 6 patients. Glomerular filtration rate (GFR) was stable following R1-PRRT. Following R2-PRRT, worsening GFR from CTCAE G2 to G3 was seen in 10% (2/20) of patients, but none after R3-PRRT. Grade 3 thrombocytopenia occurred in 2 patients after R1-PRRT and in 1 patient after R3-PRRT. Grade 4 thrombocytopenia was observed in 1 patient post R1-PRRT. Following R1-PRRT, RECIST 1.1 responses CR, PR, SD was 0%, 10%, 76%, respectively. Disease control rate on GaTate PET/CT was 52/58 (89%) post R1-PRRT. Median progression free survival (PFS) following R1-PRRT was 1.6 years (95% CI:1.2-2.3).

Conclusion: R-PRRT is feasible, tolerable and efficacious in achieving disease control in patients with progressive GEP NET.

Keywords: DOTATATERe-Treatment; Gastroenteropancreatic (GEP); Neuroendocrine neoplasms (NENs); PRRTLutetium-177.

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Conflict of interest statement

Declarations. Human ethics and consent to participate declarations: Not applicable. Conflict of interest: No direct conflicts of interests with the current research work.

Figures

Fig. 1
Fig. 1
Selection of patients for the analysis
Fig. 2
Fig. 2
PFS median survival following I-PRRT and R1-PRRT
Fig. 3
Fig. 3
Legend: A 62 year male with metastatic pNET G2 at diagnosis progressed to G3, had undergone chemotherapy with Carboplatin / Etoposide prior to I-PRRT. He underwent R-PRRT treatments (shown up to R3 in the images above) for imaging progression on several occasions with good partial response to each treatment. A total of 5 R-PRRT treatments were administered before the disease was deemed radio-resistant and further second line chemotherapy (CAPTEM) was administered almost 12 years after the I-PRRT.
See this image and copyright information in PMC

References

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Supplementary concepts