Re-treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE of patients with progressive neuroendocrine neoplasm.

Background: Neuroendocrine neoplasms (NENs) are heterogeneous groups of tumours derived from neuroendocrine cells of the ectoderm or endoderm. They are considered rare, with an estimated incidence and prevalence of 6/100,000 and 35/100,000 respectively, and a noticeable upward trend. Radioligand therapy (RLT) using beta-radiation-emitters combined with somatostatin analogues is an effective and relatively safe treatment method. It is usually used as a second-line therapy in case of progressive disease.

Material and methods: In retrospective analysis covering eight years of observation (2015-2023) of patients treated in a single highest-reference NEN centre, a subgroup of 13 who received RLT re-treatment (¹⁷⁷Lu or ¹⁷⁷Lu/⁹⁰Y-mixture) was identified. Epidemiological aspects, renal, hepatic, haematological parameters and chromogranin A serum concentration were analysed.

Results: The median PFS after the first cycle of RLT was 53.8 months (IQR = 19.3). Directly after the second cycle of RLT disease stabilization and progression was observed in 11/13 (84.6%) and 2/13 (15.4%) patients respectively. After the second cycle of RLT median observation time for the study group was 16.2 months. Eight out of 13 patients were reachable for long-term observation and stabilization was confirmed in 62.5 % (5/8), progression in 12.5% (1/8) and death in 25% (2/8) patients. Median survival time in patients with confirmed death was 7 months. During observation, an increase in creatinine concentration with a decrease in glomerular filtration rate (GFR) was noticed, however, the values were at a statistical trend level (p = 0.056; p = 0.071). The increase of liver parameters was statistically, but not clinically significant. The decrease in albumin concentration and fasting glucose concentration were not significant. An increase in chromogranin A concentration correlated, although not statistically, with the progression of the disease. A statistically significant decrease in the number of all bone marrow cell lines was observed. The first RLT cycle caused a higher decrease in blood parameters than the second. There were no differences in PFS or laboratory parameters depending on the radioligand ([¹⁷⁷Lu]Lu-DOTA-TATE vs. [¹⁷⁷Lu]Lu-DOTA-TATE/[⁹⁰Y]Y-DOTA-TATE).

Conclusions: In follow-up after RLT re-treatment stabilization was observed in 62.5%, progression in 12.5% and death in 25% of patients. Decrease of glomerular filtration, and bone marrow parameters resulted from the cumulative adverse effect of RLT, the natural ageing process, and the progression of the disease. Side effects were mainly caused by the first treatment cycle. There was no significant influence on the measured parameters, depending on the radioisotope used. Re-treatment of RLT seems to be a reliable and relatively safe method, thus should be considered in patients who underwent one cycle of RLT and responded to the treatment.