Search Results (6)

Background: Cardiotoxicity remains a concern across cancer therapies. To date, there is a lack of extensive studies evaluating the potential impact of radioligand therapy (RLT) on myocardial injury in patients with neuroendocrine tumors (NETs), particularly in subgroups with increased susceptibility to such injury. This study aimed to assess the potential cardiotoxic effects and myocardial dysfunction associated with RLT using both [¹⁷⁷Lu]Lu-DOTA-TATE and tandem therapy with [¹⁷⁷Lu]Lu-DOTA-TATE/[⁹⁰Y]Y-DOTA-TATE in patients with NETs, including specific high-risk subgroups such as patients with pre-existing heart failure, carcinoid heart disease or those previously treated with chemotherapy, by monitoring serum concentration of troponin I, CK-MB, and NT-proBNP before and after RLT. Methods: We conducted a retrospective observational analysis of 60 consecutive NET patients who underwent 228 RLT courses. A comprehensive cardiac assessment, including a detailed medical history, was performed. Additionally, serum troponin I, CKMB and NT-proBNP concentrations were measured prior to treatment and 48 h post-therapy. Fifty-two patients received [¹⁷⁷Lu]Lu-DOTA-TATE monotherapy, while eight patients were treated with tandem therapy. Results: No increase in cardiotoxicity markers was observed in the overall study population following RLT administration (ΔTroponin −0.2 [−1.4–0.3]ng/L, p = 0.007; ∆CKMB 0.0 [−4.0–3.0]U/L, p = 0.90; ΔNT-proBNP 4.0 [−45.6–33.6]pg/mL) as well as in the subgroup receiving tandem therapy (ΔTroponin 0.7 [−1.7–013]ng/L, p = 0.68; ΔCKMB −0.5 [−10.7–3.0]U/L, p = 0.21; ΔNT-proBNP −21.6 [−44.1–16.7]pg/mL). Furthermore, none of the predefined patient subgroups exhibited signs of cardiotoxicity or evidence of myocardial dysfunction. Conclusions: RLT is a safe anticancer treatment option for patients with NETs in terms of cardiotoxicity and cardiac dysfunction, including those at higher risk of cardiovascular complications. Full article

Background/Objectives: The augmentation of [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [²²⁵Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [¹⁸F]FDG PET/CT-derived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT in n = 33 patients with insufficient response on [¹⁷⁷Lu]Lu-PSMA-617 monotherapy. Methods: Six different molecular imaging parameters at baseline, i.e., before initiation of PSMA tandem RLT with respect to SUV_max, SUV_peak, SUV₅, SUV_mean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were tested for association with response and overall survival (OS). Results: After the initiation of augmentation, 24.2% of patients with a previously insufficient response experienced partial remission, and 39.4% experienced stable disease. The median OS was 7 months (95% CI: 4–11 months). None of the tested parameters were able to predict the response (all p > 0.529). In contrast, the [¹⁸F]FDG PET/CT-derived whole-body molecular imaging parameter TLG was significantly (p = 0.029) associated with OS of patients undergoing [²²⁵Ac]Ac-PSMA-617 augmented [¹⁷⁷Lu]Lu-PSMA-617 RLT after insufficient response to [¹⁷⁷Lu]Lu-PSMA-617 monotherapy. Conclusion: Implementing [¹⁸F]FDG PET/CT in the management of PSMA-RLT in clinical practice may contribute to outcome prediction and provide a route to more individualized management in mCRPC. Full article

Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). Materials and Methods: A total of 127 patients with progressive neuroendocrine neoplasms underwent RLT—4 courses, administered every 10 weeks—with the use of 7.4 GBq [¹⁷⁷Lu]Lu-DOTA-TATE or tandem therapy with 1.85 GBq [¹⁷⁷Lu]Lu-DOTA-TATE and 1.85 GBq [⁹⁰Y]Y-DOTA-TATE. Assessment of short- and long-term complications, as well as the calculation of progression-free survival (PFS) and overall survival (OS) were performed. Results: RLT caused a statistically but not clinically significant decrease in blood morphology parameters during both short- and long-term observations. Glomerular filtration rate (GFR) significantly decreased only in a long-term observation after RLT; however, it was clinically acceptable. Computed predictions of progression-free survival (PFS) and overall survival (OS) indicated that five years post-RLT, there is a 74% chance of patients surviving, with only a 58.5% likelihood of disease progression. Conclusions: Computed predictions of PFS and OS confirmed treatment efficiency and good patient survival. RLT should be considered a safe and reliable line of treatment for patients with progressive NENs as it causes only a low number of low-grade adverse events. Full article

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. Full article

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [¹⁷⁷Lu]Lu-PSMA- (¹⁷⁷Lu-PSMA) or [²²⁵Ac]Ac-PSMA-radioligand treatment (²²⁵Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received ¹⁷⁷Lu-PSMA and/or ²²⁵Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received ¹⁷⁷Lu-PSMA radioligand and two patients received tandem treatment with both ¹⁷⁷Lu-PSMA and ²²⁵Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq ¹⁷⁷Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received ²²⁵Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up. Full article

Background: Neuroendocrine neoplasms are a group of tumors deriving from neural crest. They can be located in every tissue, but most commonly in gastrointestinal tract. Targeted therapy with use of radionuclides is an available and acceptable way of treatment, but its long-term safety is still to be determined, especially with sensitive methods. Methods: Study was performed on a group of 42 patients. They underwent full cycle (4 courses; 8–12 weekly intervals) of radioligand therapy with [¹⁷⁷Lu]Lu-DOTATATE alone or tandem therapy with [¹⁷⁷Lu]Lu-DOTATATE+[⁹⁰Y]Y-DOTATATE. Late and long-term marrow and renal complications were assessed. Analysis focused on comparing data before first, fourth, and one year after the last course of RLT. Results: Study showed decreasing of all blood parameters in long-term observation, especially in lymphocytes line. Type of radioisotope, other diseases, primary tumor location, BMI, gender or age did not affect results. The only factor that had influence on hemoglobin and erythrocytes was decreased renal filtration. In long-term observation almost 10% decrease of renal filtration was observed. Type of isotope, gender, age, BMI did not affect these results. Moreover, reduction of urine IL-18, KIM-1, and albumin concentration has been observed. Conclusions: Though low-grade complications of radioligand therapy are possible, it stay a safe method of NEN treatment where benefits outweigh the risk. Full article