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

Abstract

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.

Keywords: 177Lu; 90Y; NEN; PRRT; RLT; epidemiology; incidence; neuroendocrine neoplasms.

Figure 1

Gender distribution in NEN grading subgroups.

Figure 2

Distribution of primary tumor localization.

Figure 3

Distribution of primary tumor localization in locations other than GEP-NEN.

Figure 4

Radioisotope distribution in different NEN grading (in black boxes: number of patients).

Figure 5

Non-surgical NEN tumor location.

Figure 6

Detailed distribution of somatostatin analogs used in the study group (in black boxes: number of patients).

Figure 7

Details of comorbidities (=metabolic risk factors) in the study group (white text—number of patients).

Figure 8

Map of Poland with marked referral regions. Number of patients referred from the center located in this region.

Figure 9

Kaplan–Meyer plot of the study group depending on primary tumor location.