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

Deposition of Thin Films Composed of Fe 81 BB 13.5 Si 3.5 Co 2 Material by PLD Method Using the ArF Excimer Laser

Depositions of thin films, composed of Fe 81 BB 13.5 Si 3.5 Co 2 material were performed with ArF excimer laser (λ = 193 nm). The material, with expected large magnetoelastic coefficient is potentially applicable in sensor and actuator technology. Depositions were done on polished <100> orientation Si substrates held at different temperatures: RT, 250 C, 450 C and 550 C. Results of AFM, MFM, SEM, EDS and FTIR measurements of the layers as a function of process parameters, in particular of the substrate temperature, are presented

Evaluation of morphology, mechanical properties and adhesion of boron nitride thin films produced using pulsed laser deposition

The article presents preliminary results of investigation on morphology (AFM, FTIR) of boron nitride thin films deposited onto steel substrates using PLD method. Mechanical properties (hardness and elastic modulus) of the coatings and their adhesion to the substrates were measured.On the basis of obtained results, the possibility of using steel as a substrate for pulsed laser depositionof BN films was confirmed.[b]Keywords[/b]: thin films, boron nitride, nanohardness, critical loa

Pulsed laser deposition of magnesium-doped calcium phosphate coatings on porous polycaprolactone scaffolds produced by rapid prototyping

Polycaprolactone (PCL) is a biodegradable and biocompatible polyester whose low melting point facilitates production of 3D porous scaffolds with precisely defined dimensions and internal architecture by rapid prototyping techniques. To improve the suitability of such PCL scaffolds for bone regeneration applications, they were coated with inorganic layers of calcium phosphate (CaP) and CaP doped with 0.6% w/v magnesium (CaP+Mg) using pulsed laser deposition (PLD) and characterized in vitro using osteoblast-like Saos-2 cells. Saos-2 cells were able to adhere to all scaffolds. CaP+Mg coatings significantly increased activity of alkaline phosphatase (ALP), an early differentiation marker, after 7 days. However, gene expression of ALP after 7 days was markedly lower on the same scaffolds. These data show the feasibility of coating PCL with CaP layers by PLD and the possibility of influencing osteoblastic differentiation by magnesium doping of the CaP coating

Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [¹⁷⁷Lu]Lu-DOTA-TATE or [¹⁷⁷Lu]Lu-DOTA-TATE and [⁹⁰Y]Y-DOTA-TATE—A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center

Neuroendocrine neoplasms (NENs) are a group of neoplasms arising from neuroendocrine cells. The worldwide incidence and prevalence of the NENs are estimated to be 6/100,000 and 35/100,000, respectively. Those numbers are increasing every decade, requiring higher and higher diagnosis and treatment costs. Radioligand therapy (RLT) using beta-emitting radioisotopes is an efficient and relatively safe method of treatment, typically used as a second-line treatment. RLT tolerability is higher than other available pharmacotherapies (chemotherapy or tyrosine kinase inhibitors). Recent studies show an increase in overall survival among patients treated with RLT. The present study aimed to learn the epidemiology of NENs in Poland and assess the effectiveness of RLT in a high-reference center. A prospective analysis of 167 patients treated with RLT in one of Poland’s highest-reference NEN centers was performed. The analysis covered 66 months of observation (1 December 2017–30 May 2023), during which 479 RLT single administrations of radioisotope were given. The standard procedure was to give four courses of [177Lu]Lu-DOTA-TATE alone, or tandem therapy—[177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE. Grading analysis showed that most patients had non-functioning G2 NEN with a mean Ki-67 of 6.05% (SD ± 6.41). The most common primary tumor location was the pancreas. Over two-thirds of patients did undergo surgery due to primary tumors or distant metastases. The majority of patients were using lanreotide as a chronically injected somatostatin analog. Median progression-free survival (PFS) on somatostatin analogs was 21.0 (IQR = 29.0) months. Directly after the last course of RLT, disease stabilization was noted in 69.46% of patients, partial regression was noted in 20.36% of patients, complete regression was noted in 0.60% of patients, and progression was noted in 9.58% of patients. In long-term follow-up, the median observation time among patients who underwent four treatment cycles (n = 108) was 29.8 (IQR = 23.9) months. Stabilization of the disease was observed in 55.56% of the patients and progression was observed in 26.85% of the patients, while 17.59% of patients died. Median PFS was 29.3 (IQR 23.9), and the median OS was 34.0 months (IQR 16.0). The mean age of NEN diagnosis is the sixth decade of life. It takes almost three years from NEN diagnosis to the start of RLT. In long-term observation, RLT leads to disease stabilization in over half of the patients with progressive disease. No differences in PFS or OS depend on the radioisotope used for RLT. In Poland, organized coordination of NEN treatment in high-reference centers ensures the continuity of patient care