Objectives To assess the performance of 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in metastatic gastroenteropancreatic neuroendocrine tumor (GEP-NET) and correlate it with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics.
Materials and methods Fifty patients (M : F 33 : 17, age: 26 – 71 years) with histopathologically confirmed metastatic/inoperable NETs who had undergone at least three cycles of PRRT with 177Lu-DOTATATE were included in the analysis. As part of the pretreatment evaluation, they underwent either 99mTc-HYNIC TOC (n = 40)/68Ga-DOTATATE PET (n = 10) or fluorine-18-luorodeoxyglucose (18F-FDG) PET-computed tomography (CT). Response was assessed after three and five cycles PRRT on the basis of three parameters: (a) symptomatic and subjective scale, (b) biochemical tumor marker level, and (c) objective imaging (18F-FDG/68Ga DOTATATE PET/CT, 99mTc-HYNIC TOC, ceCT), and was categorized using predefined criteria (detailed in methods).
Stable disease on imaging assessment with response on symptomatic or biochemical tumor marker scales or both were included in the responder group.
Results The study population was broadly classified into (a) metastatic GEP-NET with known primary (n = 43 i.e. 86%), which was further subclassified according to the site of primary and (b) those with unknown primary (n = 7 i.e.14%). Symptomatic response: 96% of patients showed a symptomatic response or improvement in health-related quality of life, irrespective of tumor proliferation index, dual tracer imaging characteristics, and response or progression of disease in the scan. Biochemical tumor marker response: 83% of scan responders showed a decrease, 10% showed a stable value, and 7% showed an increase in tumor marker levels. Among the scan nonresponders, 67% patients showed a corresponding increase in the tumor marker level, 22% patient showed a decrease, whereas 11% showed stable values. Scan response: 31 out of total 50 patients (62%) showed a partial scan response with either a decrease in the number of somatostatin receptor (SSTR)-positive lesions or metabolic activity in 18F-FDG/68Ga-DOTATATE PET-CT or both, 10 patients (20%) showed stable disease, and nine patients (18%) showed progressive disease. The higher objective partial scan response documented can be explained by the introduction of the 18F-FDG-PET/CT parameter as a determinant criterion. Among the responders category (n = 41), 32 (78.04%) showed discordance between 18F-FDG-PET/CT-based and SSTR-based imaging, whereas eight out of nine patients with nonresponse category (88.89%) showed concordance between SSTR-based imaging and 18F-FDG-PET/CT. Conversely, 32 of 33 patients (96.97%) with SSTR/ 18F-FDG discordance and nine out of 17 (52.94%) with concordance were finally classified as responders, whereas the remaining, that is, 1/33 (3.03%) in the ‘discordant’ category and 8/17 (47.06%) with imaging concordance were classified as nonresponders, respectively.
Conclusion Our data show that high pretherapy 18F-FDG maximum standardized uptake values were associated with increased chances of treatment refractoriness in GEP-NETs. However, symptomatic improvement was observed in most cases irrespective of grade and 18F-FDG uptake. High pretherapy 18F-FDG maximum standardized uptake value in both low-grade and high-grade NET predicted a poor outcome and was associated with disease progression. Introduction of 18F-FDG-PET/CT parameter as a determinant of response classification increases the percentage of objective scan responders among patients with grades I and II GEP-NETs as 18F-FDG activity was observed to decrease before SSTR-based imaging and more frequently compared with the latter.