RESUMEN
PURPOSE: The aim of this retrospective analysis is to estimate the most appropriate single cycle and cumulative doses of 225Ac-DOTATOC in patients treated for somatostatin-receptor-expressing cancers. METHODS: 225Ac-DOTATOC was administered to thirty-nine patients with various somatostatin-receptor-positive tumors. Baseline and follow-up 68Ga-DOTATOC PET/CT, lab tests, and renal scintigraphy were obtained. Patients received long-term follow-up either at the local cancer center or in close collaboration with external oncologists. Acute and chronic hematological toxicity was evaluated quantitatively over time. Long-term follow-up of creatinine was used to approximate the annual loss of estimated GFR (eGFR). RESULTS: Dose-dependent acute hematological toxicity was seen at single doses above 40 MBq or repeated doses greater than approximately 20 MBq 225Ac-DOTATOC at 4 month intervals. Treatment-related kidney failure occurred in 2 patients after a delay of >4 years but was independent of administered radioactivity, and other clinical risk factors were important contributors to renal decline. In general, the annual decline of eGFR among patients did not follow a clear dose-effect relationship even in patients with previous ß-therapy. An average eGFR-loss of 8.4ml/min (9.9%) per year was observed which is similar to the experience with ß-therapy studies. CONCLUSION: Treatment activities of approx. 20 MBq per cycle (4 monthly repetition) and cumulative doses up to 60-80 MBq generally avoided both acute and chronic grade 3/4 hematotoxicity in patients with advanced stage malignancies. Chronic renal toxicity was observed at these doses, but pre-existing renal risk factors were important co-factors. These data represent a starting point for additional research to more precisely define safety thresholds of 225Ac-DOTATOC.
Asunto(s)
Tumores Neuroendocrinos , Insuficiencia Renal , Estudios de Seguimiento , Humanos , Octreótido/efectos adversos , Octreótido/análogos & derivados , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos/efectos adversos , Estudios Retrospectivos , Somatostatina , Tomografía Computarizada por Rayos XRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) may arise from intraductal papillary mucinous neoplasms (IPMN) with malignant transformation, but a significant portion of IPMN remains to show benign behavior. Therefore, it is important to differentiate between benign IPMN and IPMN lesions undergoing malignant transformation. However, nonoperative differentiation by ultrasound, CT, MRI, and carbohydrate antigen 19-9 (CA19-9) is still unsatisfactory. Here, we assessed the clinical feasibility of additional assessment of malignancy by PET using 68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI PET) in 25 patients with MRI- or CT-proven cystic pancreatic lesions. Methods: Twenty-five patients with cystic pancreatic lesions who were followed up in the European Pancreas Center of Heidelberg University hospital and who were led to surgical resection or fine-needle aspiration due to suspicious clinical, laboratory chemistry, or radiologic findings were examined by static (all patients) and dynamic (20 patients) 68Ga-FAPI PET. Cystic pancreatic lesions were delineated and SUVmax and SUVmean were determined. Time-activity curves and dynamic parameters (time to peak, K 1, k 2, K3, k 4) were extracted from dynamic PET data. Receiver-operating curves of static and dynamic PET parameters were calculated. Results: Eleven of the patients had menacing IPMN (high-grade IPMN with [6 cases] or without [5 cases] progression into PDAC) and 11 low-grade IPMN; 3 patients had other benign entities. Menacing IMPN showed significantly elevated 68Ga-FAPI uptake compared with low-grade IPMN and other benign cystic lesions. In dynamic imaging, menacing IPMN showed increasing time-activity curves followed by slow decrease afterward; time-activity curves of low-grade IPMN showed an immediate peak followed by rapid decrease for about 10 min and slower decrease for the rest of the time. Receiver-operating curves showed high sensitivity and specificity (area under the curve greater than 80%) of static and dynamic PET parameters for the differentiation of IPMN subtypes. Conclusion: 68Ga-FAPI PET is a helpful new tool for the differentiation of menacing and low-grade IPMN and shows the potential to avoid unnecessary surgery for nonmalignant pancreatic IPMN.
Asunto(s)
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Quiste Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radioisótopos de Galio , Neoplasias Intraductales Pancreáticas/diagnóstico por imagen , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Páncreas , Neoplasias PancreáticasRESUMEN
Accurate detection of malignant transformation and risk-stratification of intraductal papillary mucinous neoplasms (IPMN) has remained a diagnostic challenge. Preliminary findings have indicated a promising role of positron emission tomography combined with computed tomography and 18F-fluorodeoxyglucose (18F-FDG-PET/CT) in detecting malignant IPMN. Therefore, the aim of this model-based economic evaluation was to analyze whether supplemental FDG-PET/CT could be cost-effective in patients with IPMN. Decision analysis and Markov modeling were applied to simulate patients' health states across a time frame of 15 years. CT/MRI based imaging was compared to a strategy with supplemental 18F-FDG-PET/CT. Cumulative costs in US-$ and outcomes in quality-adjusted life years (QALY) were computed based on input parameters extracted from recent literature. The stability of the model was evaluated by deterministic sensitivity analyses. In the base-case scenario, the CT/MRI-strategy resulted in cumulative discounted costs of USD $106,424 and 8.37 QALYs, while the strategy with supplemental FDG-PET/CT resulted in costs of USD $104,842 and a cumulative effectiveness of 8.48 QALYs and hence was cost-saving. A minimum specificity of FDG-PET/CT of 71.5% was required for the model to yield superior net monetary benefits compared to CT/MRI. This model-based economic evaluation indicates that supplemental 18F-FDG-PET/CT could have a favorable economic value in the management of IPMN and could be cost-saving in the chosen setting. Prospective studies with standardized protocols for FDG-PET/CT could help to better determine the value of FDG-PET/CT.