Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors-Extended Analysis of Potential Acute and Chronic Complications.

Neuroendocrine tumors (NEN) are a group of neoplasms that arise from hormonal and neural cells. Despite a common origin, their clinical symptoms and outcomes are varied. They are most commonly localized in the gastrointestinal tract. Targeted radioligand therapy (RLT) is a treatment option which has proven to be successful in recent studies. However, the possible outcomes and true safety profile of the treatment need to be fully determined, especially by new, more sensitive methods. Our study aimed to present an extended analysis of acute and chronic renal complications during and after radioligand therapy using, for the first time in the literature, innovative and complex renal parameters. Forty patients with neuroendocrine tumors underwent four courses of radioligand therapy with [177Lu]Lu-DOTATATE or [177Lu]Lu/[90Y]Y-DOTATATE. Radioisotopes were administrated in intervals of 8-12 weeks, with concurrent intravenous nephroprotection. New detailed and sensitive renal parameters were used to determine the renal safety profile during and after radioisotope therapy for standard treatment of NEN. During the first and fourth courses of RLT, no change in the glomerular filtration rate (GFR) was observed. However, long-term observations one year after the treatment showed a 10% reduction in the GFR. During the first course of treatment, the fractional urea and calcium excretions increased, while the fractional potassium concentration decreased. The fractional calcium excretion remained highly increased in long-term observations. Decreases in urine IL-18, KIM-1 and albumin concentrations were observed during RLT. The concentrations of IL-18 and KIM-1 remained low even a year after therapy. The ultrasound parameters of renal perfusion changed during treatment, before partially returning to the baseline one year after therapy, and were correlated with the biochemical parameters of renal function. A permanent increase in diastolic blood pressure was correlated with the decrease in the GFR observed during the study. In this innovative and complex renal assessment during and after RLT, we found a permanent 10% per year decrease in the GFR and noticeable disturbances in renal tubule function. The diastolic blood pressure also increased.

Renal Cortical Perfusion Estimated in Color Doppler Dynamic Tissue Perfusion Measurement in Patients Treated with Levothyroxine Following Total Thyroidectomy for Resectable Thyroid Cancer Is Independently Associated with Free Thyroxine: A Single-Center Prospective Study.

BACKGROUND The thyroid state significantly influences renal function. However, a direct link between thyroid and kidney dysfunction has not been identified. Thyroid hormones affect cardiac output and vascular resistance, and thus can modify kidney perfusion. This prospective study aimed to test the association between renal cortical perfusion (RCP) estimated in color Doppler sonographic dynamic tissue perfusion measurement (DTPM) with thyroid hormones in 36 patients treated with levothyroxine following total thyroidectomy for resectable thyroid cancer. MATERIAL AND METHODS Blood tests, blood pressure monitoring, and DTPM of the renal cortex were performed. To exclude possible reading errors, the intrarater reliability of the ultrasound perfusion measurement method was estimated. RESULTS The absolute difference between the 2 ultrasound RCP measurements was 5.2±4.4%. RCP correlated significantly with free thyroxine (FT4) (r=0.46; p=0.006) but not with triiodothyronine and thyroid-stimulating hormone. In the adjusted to age backward stepwise multivariable regression analysis model, including estimated glomerular filtration rate, mean arterial pressure, and FT4, only FT4 was independently associated with RCP (R²=0.21; p=0.006). CONCLUSIONS Renal cortical perfusion is independently associated with free thyroxine, which can contribute to renal function abnormalities in the condition of impaired thyroid function. This small prospective study from a single center showed that the renal cortex's color Doppler sonographic dynamic tissue perfusion measurement had very good intraobserver reproducibility.

Impact of Radioiodine Treatment on Doppler Flow Parameters in the Central Retinal Artery and Ophthalmic Artery in Patients With Hyperthyroidism.

OBJECTIVES: The aim of this study was to identify changes in Doppler flow parameters in the central retinal artery (CRA) and ophthalmic artery (OA) that could be indicative of de novo development of thyroid-associated orbitopathy in the early period after radioiodine treatment. METHODS: Eighty-two patients with hyperthyroidism were enrolled: 44 with Graves disease and 38 with toxic nodular goiter. In both groups, blood flow parameters in the CRA and OA were analyzed before and 2 and 4 weeks after radioiodine administration. The peak systolic velocity and end-diastolic velocity (EDV) were evaluated, and the resistive index (RI) was calculated. RESULTS: There were no statistically significant differences in the peak systolic velocity, EDV or RI between groups at baseline and 4 weeks after radioiodine administration. Two weeks after radioiodine administration, the RI in the CRA (P = .034) and EDV in the OA (P = .026) were significantly lower, and the EDV in the CRA (P = .004) was higher in patients with Graves disease than in patients with toxic nodular goiter. There was an inverse correlation between baseline thyrotropin receptor autoantibody (TRAb) levels and the difference between the RI at weeks 4 and 2 (RI3-RI2) in the CRA (r = -0.458; P < .05) and a positive correlation between the baseline anti-thyroid peroxidase antibody concentration and RI3-RI2 in the OA (r = 0.435; P < .05). CONCLUSIONS: Administration of radioiodine results in more prominent features of hyperkinetic circulation. Patients with Graves disease and high TRAb titers have a lower sensitivity to radioiodine treatment. High TRAb titers suggest higher disease activity and a weaker therapeutic effect of radioiodine.

Tandem peptide receptor radionuclide therapy using 90Y/177Lu-DOTATATE for neuroendocrine tumors efficacy and side-effects - polish multicenter experience.

INTRODUCTION: One of the concepts of theranostics in nuclear medicine is peptide receptor radionuclide therapy (PRRT), whereby labeled somatostatin analogs are used for imaging and treating inoperable or disseminated neuroendocrine tumors (NET). AIM: The aim of the study was to determine the therapeutic efficacy and toxicity of tandem 90Y /177Lu-DOTATATE in patients with disseminated NET in a multicenter trial. MATERIALS AND METHODS: 103 patients with NET G1/G2 treated with 90Y/177Lu-DOTATATE (1:1) with amino-acid infusion for nephroprotection were included in the study. RESULTS: Overall survival from the disease diagnosis (OS-D) was 127.4 months and from the time of PRRT (OS-T) was 89.5 months. Progression-free survival (PFS) was 29.9 months. An analysis based on the proliferation index revealed a statistically significant impact on PFS and OS-T (PFS G1 vs G2, 59.3 vs 24.3 months; OS-T G1 vs G2, not reached vs 79.9 months). The effect of the primary disease site was also analyzed. For pancreatic vs small bowel vs large bowel, the PFS was 30.8 vs 30.3 vs 40.6 months, the OS-T was 94 vs 61.9 vs 131.2 months and OS-D was 130.4 vs 89.2 vs not reached months, respectively. The 2-year risk of progression was 42%. The probability of 2-year and 5-year overall survival was 89% and 62%, respectively. PRRT was well tolerated by all patients. One patient (1%) developed myelodysplastic syndrome. No other grade 3 and 4 hematological or renal toxicity was observed. CONCLUSIONS: This multicenter trial showed that tandem 90Y/177Lu-DOTATATE is highly effective and safe therapy for patients with disseminated NET.

THE ROLE OF PET/CT WITH 11C-METHIONINE IN CONTEMPORARY NUCLEAR MEDICINE.

OBJECTIVE: Positron emission tomography (PET/CT) is a non-invasive molecular imaging technique using isotopes with a short half-life usually in combination with chemical compounds. The most commonly used PET/CT tracer is 2-fluoro-2-deoxy-D-glucose labeled with fluorine (18-FDG). It is used mainly in oncological diagnostics as well as myocardial viability, epilepsy and inflammatory diagnostics. The tracer less commonly used in PET/CT could be carbon-labeled methionine (11C-MET). It is mainly used in the diagnosis of focal lesions in the central nervous system. There are also reports of the use of this tracer in diagnostics of the primary, secondary and tertiary hyperparathyroidism as well as multiple myeloma. This tracer may also be used in the diagnosis of lymphoproliferative diseases and solid tumors, although there is no clear evidence of its advantage over 18-FDG. CONCLUSION: Conclusion: Significant difficulties in the production and transport of this tracer and lack of reimbursement of this type of procedure in Poland limits the use of this tracer for scientific research.

Role of Nitric Oxide Pathway in Development and Progression of Chronic Kidney Disease in Rats Sensitive and Resistant to its Occurrence in an Experimental Model of 5/6 Nephrectomy.

BACKGROUND Understanding the mechanisms conditioning development of chronic kidney disease (CKD) is still a challenge. The aim of this study was to evaluate the activity of the intrarenal nitric oxide (NO) pathway in the context of sensitivity or resistance of different animal strains to the development and degree of renal failure. MATERIAL AND METHODS Two rat strains were used: Wistar (WR) and Sprague-Dawley rats (SDR) in a model of CKD - 5/6 nephrectomy. We assessed parameters of renal failure and expression of nitric oxide synthase (NOS) isoforms in renal cortex and medulla. RESULTS We did not observe renal failure in WR, and CKD developed in SDR with increase of creatinine and urea concentration as well as decrease of diuresis and glomerular filtration. In the renal cortex, baseline expression of NOS2 was higher in WR than in SDR. 5/6 nephrectomy resulted in reduction of NOS2 in both strains and NOS3 in WR. In the renal medulla, baseline NOS2 expression was higher in SDR, and nephrectomy resulted in its decrease only in SDR. Although baseline NOS3 expression was higher in SDR, the NOS3 expression after nephrectomy was higher in WR rats. CONCLUSIONS In model of CKD - 5/6 nephrectomy, SDR proved to be sensitive and WR resistant to development of CKD. The intrarenal activity of the nitric oxide pathway was the factor that differentiated both strains. This mechanism may be responsible for insensitivity of WR to development of renal failure in this model of CKD.

Left ventricular end-diastole hemodynamics is strongly associated with spontaneous cardiac baroreflex in humans.

BACKGROUND: In animals, hemodynamic conditions during left ventricular (LV) end-diastole are crucial for the excitation of autonomic afferents distributed throughout cardiac chambers and large thoracic vessels. The objective of the study was to select the echocardiographic indices of LV diastolic function that are the most potent predictors of the heart's spontaneous baroreflex in humans. METHODS: In 47 untreated hypertensive patients (26 with normal and 21 with increased left atrium diameter) and 24 healthy controls, baroreflex sensitivity (BRS) was assessed in the low (αLF; 0.04-0.15 Hz) and high frequency (αHF; 0.15-0.4 Hz) components in the supine and during tilting. The [Formula: see text] normalized to LV end-diastolic diameter (the [Formula: see text] index) is a marker of the septum late diastolic distension rate ([Formula: see text] denotes peak late diastolic velocity at the septal mitral annulus) under the corresponding transmitral pressure gradient that determines the peak velocity of blood flow (A) into the LV chamber. RESULTS: The [Formula: see text] markedly stronger than [Formula: see text] ratio correlated with the BRS. In the best-fit models of multivariable linear regression, the [Formula: see text] index was the independent predictor of the αLF BRS at tilting (ß = -0.3; p = 0.01). Independent of clinical and echocardiographic parameters, the [Formula: see text] index predicted also both the αHF BRS in the supine position (ß = -0.23; p = 0.01) and the αHF BRS reinforcement due to increased preload (ß = -0.28; p = 0.001). CONCLUSIONS: The [Formula: see text] index is a reliable marker of diastolic dysfunction that evokes significant heart's baroreflex impairment and is markedly stronger than [Formula: see text] ratio associated with these systemic consequences of altered LV diastole hemodynamics.

Current treatment options for gastroenteropancreatic neuroendocrine tumors with a focus on the role of lanreotide.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a large and very diverse group of neoplasms. Clinical presentation of NETs depends on the site of the primary tumor and whether the tumor is functioning (i.e., secreting peptides or neuroamines that produce symptoms). The diagnosis of GEP-NET is further complicated by symptomatic differences that occur depending on the type of secreted peptide or neuroamine. Due to their heterogeneity and unique characteristics, early diagnosis of GEP-NETs is difficult, which increases the likelihood of metastatic disease and reduces the scope of therapeutic possibilities. Thus, a multidisciplinary approach for the treatment of GEP-NETs is necessary. This review is the result of presentations that were delivered during an expert meeting on the treatment of GEP-NETs supported by Ipsen. We summarize the current knowledge on the epidemiology, incidence, diagnosis, and treatment of GEP-NETs. We examined the role of the somatostatin analog (SSA) lanreotide and the impact of the data from the recently published, randomized, double-blind, placebo-controlled CLARINET study (Controlled study of Lanreotide Antiproliferative Response In Neuroendocrine Tumors) on disease management. We also review the recent treatment options and recommendations for GEP-NETs.

Ectopic Cushing's syndrome in light of modern diagnostic techniques and treatment options.

Ectopic adrenocorticotropic hormone secretion (EAS) is responsible for approximately 10-15% cases of Cushing's syndrome. EAS is associated with various tumors such as small cell lung cancer and well-differentiated bronchial or gastrointestinal neuroendocrine tumors. Hormonal diagnostics include assessments in basic conditions as well as dynamic tests, such as the high-dose dexamethasone suppression test and corticotrophin releasing hormone (CRH) stimulation test. Treatment selection depends on the type of tumor and its extent. In the case of neuroendocrine tumors, the main treatments are surgery and administration of somatostatin analogs that may be additionally radiolabeled for targeted radiotherapy. The tumor histology and the presence and control of hypercortisolemia and metastases are of major importance in prognosis. In this article we presented the principles of modern hormonal and imaging diagnostics techniques as well as the key issues associated with treatment of ACTH-dependent Cushing's syndrome due to EAS.

Can radioiodine be administered effectively and safely to a patient with severe chronic kidney disease?

Chronic kidney disease is an increasingly widespread problem. The progression of renal failure is associated with the development of various hormonal disorders, including those affecting the thyroid gland. The prevalence of multinodular goitre and differentiated thyroid cancer increases significantly in patients with renal failure. However, radioiodine treatment in patients with severe chronic kidney disease gives rise to a number of difficulties. The only conclusions regarding this treatment thus far have been derived from single case studies. It seems that prospective controlled studies can contribute to the creation of standards for radioiodine treatment in patients with various stages of chronic kidney disease, while maintaining the safety of such treatment for both patients and medical staff. This review gives the response to the question how nowadays to treat the patients with severe chronic kidney disease with radioiodine.

LanroNET, a non-interventional, prospective study to assess the resource utilization and cost of lanreotide autogel 120 mg in Polish patients with neuroendocrine tumors - results of interim analysis.

AIM OF THE STUDY: To examine characteristics and treatment patterns of symptomatic neuroendocrine tumors (NETs) patients who received lanreotide Autogel 120 mg (ATG120) administered as part of routine clinical practice. MATERIAL AND METHODS: Lanro-NET is a national, multicenter, non-interventional, observational study in the population of adult patients with symptomatic NETs treated with ATG120 for at least three months before inclusion. Data on demographic and clinical characteristics of the population, dosing interval regimen and aspects of administration were collected prospectively during 12 months. Costs were calculated from the perspective of public payer for the year 2014. RESULTS: Fifty-two patients were enrolled in the study. Primary tumors were located predominantly in gastrointestinal tract (51.2%), all tumors were metastatic. The most commonly reported disease symptoms were flushing and diarrhea (55.8% of patients). 86% of patients had undergone surgery, chemotherapy and radioisotope therapy were used in 11.6% and 46.5% of patients, respectively. During the 12-months observation 12 (28%) patients received ATG120 at an extended dosing interval (> 4 weeks), the mean number of days between injections was 31.75 (SD 6.74). The cost of ATG12 was estimated at 4273.17 PLN patient/month. In all patients ATG120 was administered by nurse, 51.6% of injections in out-patient setting, 48.4% - in hospital. CONCLUSIONS: This study presents the current use of ATG120 in the population of Polish NETs patients in a realistic clinical settings. Finding that 28% of patients could be treated with extended dose intervals supports the potential for ATG120 of reducing treatment burden.

Thyroid Cancer in Regions Most Contaminated after the Chernobyl Disaster.

Exposure to ionizing radiation, especially during childhood, is a well-established risk factor for thyroid cancer. Following the 1986 Chernobyl nuclear power plant accident the total number of cases of thyroid cancer registered between 1991 and 2015 in males and females who were less than 18 years old exceeded 19,000 (in Belarus and Ukraine, and in the most contaminated oblasts of the Russian Federation). However, as indicated by the United Nations Scientific Committee on the Effects of Atomic Radiation the fraction of the incidence of thyroid cancer attributable to radiation exposure among the non-evacuated residents of the contaminated regions of Belarus, Ukraine and Russia is of the order of 0.25. Apparently, the increased registration of thyroid neoplasms in the parts of these countries is a classical 'screening effect', i.e., massive diagnostic examinations of the risk-aware populations performed with modern eqipment resulting in detection of many occult neoplasms (incidentalomas). Moreover, one type of thyroid cancer previously called 'encapsulated follicular variant of papillary thyroid carcinoma' is non-invasive and instead of 'carcinoma' should now be recognized as 'noninvasive follicular thyroid neoplasm with papillary-like nuclear features.' Other potential causes of overdiagnosing of thyroid tumors include increase of the spontaneous incidence rate of this disease with age, iodine deficiency among children from Belarus, Russia and Ukraine, and/or consumption by these children of drinking water containing high levels of nitrates that likely coincides with the carcinogenic effect of radiation on the thyroid gland.

A nuclear beacon of hope: an advanced, metastatic glucagonoma treated with [177Lu]Lu-DOTA-TATE.

Glucagonoma is a rare pancreatic neuroendocrine tumor (panNET) that can be characterized by increased secretion of glucagon and distinguishing symptoms - glucagonoma syndrome with a typical dermatosis, necrolytic migratory erythema, being its most common manifestation. While surgery and somatostatin analogs remain first-line therapeutic options in panNETs, radioligand therapy with [177Lu]Lu-DOTA-TATE is a recommended second-line palliative treatment in advanced, metastatic cases. However, its prospects and efficacy are still not vastly researched in less frequent neuroendocrine neoplasms. Here, we present an extraordinary case of a metastatic glucagonoma treated with [177Lu]Lu-DOTA-TATE used as a second-line treatment in progressive disease.

Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC- 99mTc/EDDA)NH2]-exendin-4 for the detection of insulinoma.

PURPOSE: The objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4. METHODS: Studies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed. RESULTS: Both sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis. CONCLUSION: [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.

Polish experience in Peptide receptor radionuclide therapy.

PATIENTS AND METHODS: During the period from April 2004 to December 2010, 358 patients underwent peptide receptor radionuclide therapy (PRRT) ((90)Y-DOTATATE, (177)Lu-DOTATATE, and (90)Y/(177)Lu-DOTATATE) in Poland. RESULTS: The majority of patients underwent (90)Y-DOTATATE therapy (n = 177) with progression-free survival (PFS)/time to progression (TTP) of 17-44 months and overall survival (OS) of 22-34.2 months. Twelve-month follow-up revealed stable disease (SD) in 46-60%, disease regression (RD) in 16-35%, disease progression (PD) in 7-17%, and complete remission (CR) in 3% of patients. In patients treated with (90)Y/(177)Lu-DOTATATE (n = 44), PFS/TTP was 24.2-28.3 months and OS was 49.8-52.8 months. Twelve-month follow-up showed SD in 62-70%, RD in 15-20%, and PD in 10-12% of patients. The treatment was well tolerated. No severe adverse events occurred. Grade 3 toxicity [in leucocytes (WBC) and thrombocytes (PLT)] was seen in 6-20% of patients treated with (90)Y-DOTATATE. In that group, renal toxicity grade 3 was seen in 5-12% and grade 4 in 3-8%. In patients treated with tandem therapy with (90)Y/(177)Lu-DOTATATE or (177)Lu-DOTATATE alone, hematological and renal toxicity grade 3 or 4 was not observed. CONCLUSIONS: The results indicate that PRRT with the procedures and isotopes used is an effective and safe therapy option for patients with metastatic or inoperable neuroendocrine tumors (NETs). Our results suggest that tandem therapy with (90)Y/(177)Lu-DOTATATE provides longer overall survival than single-isotope treatment. Hematological toxicity was rare in all treated patients. Renal toxicity grade 3 and 4 was observed only in the group treated with (90)Y-DOTATATE.

Utility of non-contrast Dual Energy Computed Tomography in diagnosis of differentiated thyroid cancer - two case study.

BACKGROUND: Dual Energy Computed Tomography (DECT) is a technology that allows for viewing computed tomography spectral images. This method, due to ability of presenting specific elements and substances (like water, calcium and iodine), can be used to locate selected type of tissues. Thyroid tissue due to being rich in endogenous iodine, can be located even without administration of contrast agent. CASE PRESENTATION: In presented cases authors used a feature of accumulating endogenous iodine in thyroid derivative tissue for diagnosis of differentiated thyroid cancer metastases. In Patient One DECT was a decisive parameter qualifying for the surgery. Due to use of DECT in Patient Two it was possible to directly localize thyroid cancer metastases, which was unfeasible using standard techniques (scintigraphy and [18 F]FDG PET/CT). It helped to perform targeted biopsy and confirm diagnosis of thyroid cancer metastases, allowing to introduce treatment with sorafenibe. CONCLUSION: DECT confirmed its utility in locating thyroid tissues, including differentiated thyroid cancer (DTC) metastases. The method could be used in the future, especially in borderline or ambiguous cases with no localization of DTC in ultrasonography, RAI scintigraphy, or [18 F]FDG PET/CT, and among patients having contraindications for contrast-CT.

Difficulties in achieving euthyroid status in a patient with differentiated thyroid cancer after sleeve gastrectomy.

Not required for Clinical Vignette.

Radioligand Therapy with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE in Patients with Neuroendocrine Neoplasms of Unknown Locations, or Locations Other Than the Midgut and Pancreas as Primaries in a G1, G2 and G3 Grade.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a rare group of tumors with a different clinical course, prognosis and location. Radioligand therapy (RLT) can be used as a first or second line of treatment. It is registered in gastroenteropancreatic NENs (GEP-NENs) as grades G1 and G2. Tumors with an unknown point of origin, diagnosed outside the gastrointestinal tract and pancreas (non-GEP) or at the G3 grade, remain in the "grey area" of treatment. MATERIALS AND METHODS: Analysis of 51 patients with NENs who underwent RLT in a single highest reference center from 2018 to 2023 was performed. Treatment was administrated to the patients with neoplasms of unknown origin, non-GEP-NENs, and ones with G3 grade. In total, 35 patients received 177-Lutetium (7.4 GBq), while 16 received 177-Lutetium and 90-Yttrium with equal activities (1.85 + 1.85 GBq). RESULTS: The progression-free survival (PFS) before RLT qualification was 34.39 ± 35.88 months for the whole study group. In subgroups of patients with an unknown tumor location (n = 25), the median PFS was 19 months (IQR = 23), with "other" locations (n = 21) at 31 months (IQR = 28), and with NEN G3 (n = 7) at 18 months (IQR = 40). After RLT, disease stabilization or regression was observed in 42 (87.5% of) patients. RLT did not cause statistical changes in creatinine or GFR values. Hematological parameters (RBC, WBC, PLT, HGB) as well as chromogranin A concentration decreased significantly. There were no statistical differences between both subgroups regarding the type of radioisotope (177-Lutetium vs. 177-Lutetium and 90-Yttrium). After RLT in long-term observation, the median observation time (OT) was 14 months (IQR = 18 months). In patients with progression (n = 8), the median PFS was 20 months (IQR = 16 months), while in patients with confirmed death (n = 9), the median overall survival (OS) was 8 months (IQR = 14 months). CONCLUSIONS: Our study showed that 87.5% of NEN patients with unknown origin, non-GEP-NENs, and those with GEP-NEN G3 grade had benefited from the radioligand therapy. There were no significantly negative impacts on renal parameters. The decrease of bone marrow parameters was acceptable in relation to beneficial disease course. The decrease of chromogranin concentration was confirmed as a predictive factor for disease stabilization or regression.

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.