Safety and Efficacy of 177 Lu-DOTATATE in Neuroendocrine Tumor Patients With Extensive Bone Disease.

AIM: The aim of this study was to assess the efficacy and safety of 177 Lu-DOTATATE in patients with neuroendocrine tumors (NETs) and extensive bone metastases, that is, more than 50% of the skeleton involved. METHOD: A single-center retrospective analysis was performed in 30 patients (13 women and 17 men, mean age, 60 years; range, 35-77 years) undergoing 177 Lu-DOTATATE therapy. Patients had progressive metastatic NETs with extensive skeletal metastases (>50% skeletal involvement seen on baseline 68 Ga-DOTATATE PET/CT). The average administered activity was 7.308 (SD, 0.02) GBq per cycle with average treatment interval of 15 weeks. Survival analyses (progression-free survival [PFS], overall survival), radiological response assessment, toxicity assessment, and health-related quality of life (QoL) was performed. RESULTS: Overall, 26 patients completed 4 cycles, and 4 patients had less than 4 cycles of 177 Lu-DOTATATE. One patient (3%) did not complete treatment because of hematological toxicity. The estimated median PFS and median overall survival were calculated at 27 and 35 months, respectively. End-of-treatment radiological assessment showed partial response in 5 patients (17%), stable disease in 20 patients (66%), and radiological progressive disease in 3 patients (10%). Clinical progression was seen in a further 2 patients (7%).The incidence of grade 3/4 bone marrow toxicity was 10%. No patient had grade 3/4 peptide receptor radionuclide therapy-related nephrotoxicity. There was overall improvement in global QoL score (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Gastrointestinal NET-21) ( P = 0.019). CONCLUSION: 177 Lu-DOTATATE seems to have satisfactory therapeutic outcome in patients with advanced metastatic NET with extensive bone disease, with reasonable PFS and significant improvement in the global health-related QoL. The bone marrow toxicity was within the accepted range. Increasing the interval between cycles does not seem to reduce efficacy and may reduce toxicity, ensuring the bone marrow has sufficient time to recover between cycles.

Single centre retrospective review of outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy in the treatment of progressive metastatic neuroendocrine tumours: Survival, toxicity, and prognostic factors.

The aim of this study was to evaluate the efficacy and safety of 177 Lu-DOTATATE therapy in advanced metastatic disease. A retrospective analysis of 395 patients (180 female, 215 males, mean age 62) with progressive metastatic neuroendocrine tumours (NETs) who were treated with 177 Lu-DOTATATE was performed. Overall, 115 patients had less than four cycles and 280 completed four cycles of treatment. Progression-free survival (PFS) and overall survival (OS) was performed using Kaplan-Meier analysis. Analysis of survival predictors was performed using Cox regression model. Toxicity was defined using the Common Terminology Criteria for Adverse Events version 5 (CTCAE 5.0). The percentage of patients with liver and skeletal metastases were 91 and 57%, respectively. Median PFS and OS were calculated at 33 months (95% CI: 29-37 months) and 46 months (95% CI: 48-56 months), respectively. End of treatment response assessment was performed using cross sectional imaging demonstrated partial response in 22%, stable disease in 64% and progressive disease in 14% of patients. Overall, grade 3 and 4 bone marrow toxicity was seen in 8%. One patient (0.3%) developed irreversible grade 4 nephrotoxicity. Myelodysplastic disease was recorded in one patient (0.3%). Univariate analysis of PFS predictors showed that body mass index (BMI), baseline chromogranin A (CgA) >400 ng/l, baseline alkaline phosphatase (ALP) >130 mg/dl, liver tumour volume and overall tumour burden were significant. On multivariate analysis only Ki67, high CgA and low BMI retained significance. 177 Lu-DOTATATE is an effective treatment in advanced NETs with generally high-volume metastases. It is well-tolerated. Ki-67, CgA and BMI appear to be predictors for PFS.

Safety of Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Neuroendocrine Tumor Patients with Chronic Kidney Disease.

Our purpose was to assess the efficacy and safety of 177Lu-DOTATATE in neuroendocrine tumor patients with reduced renal function. Methods: A single-center retrospective analysis was performed on 33 patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 Of these, 26 had chronic kidney disease (CKD) stage 3a (eGFR, 45-60 mL/min/1.73 m2) and 7 had CKD 3b (eGFR, 30-45 mL/min/1.73 m2). Renal toxicity and temporal changes in eGFR were recorded. The association between potential risk factors and any kidney function deterioration (>10% reduction in eGFR) was evaluated. Data on survival, the radiologic response assessment, and quality of life were collected. Results: The incidence of permanent grade 3 or 4 nephrotoxicity was 3% (a single patient with grade 4 nephrotoxicity). The mean annual reduction in eGFR was estimated at 2.5%. A permanent decline of less than 10% in eGFR of any grade was recorded in 45% of patients (n = 15). Nine patients moved into higher CKD categories (8 patients who moved from CKD 3a to CKD 3b and 1 patient who moved from CKD 3b to CKD 5). No significant relationship was found between renal risk factors and a permanent reduction in renal function. Grade 3 or 4 bone marrow toxicity was observed in 9% of patients. The estimated median progression-free survival was 42 mo, and the median overall survival was 47 mo. At the end of treatment, the radiologic assessment showed a partial response in 33%, stable disease in 55%, and progressive disease in 12%. There was an improvement in global quality of life and endocrine score (European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Gastrointestinal NET-21) (P = 0.046 and 0.041, respectively). Conclusion: 177Lu-DOTATATE appears to be generally well tolerated in patients with preexisting CKD 3, with a low incidence of permanent major nephrotoxicity. 177Lu-DOTATATE appears to have a good therapeutic effect, with most patients reporting improvement in quality of life.

Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumours.

BACKGROUND: The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management. OBJECTIVE: The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours. METHODS: A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs). RESULTS: PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients' Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible. CONCLUSION: PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.