PT - JOURNAL ARTICLE AU - Jingjing Zhang AU - Harshad Kulkarni AU - AVIRAL SINGH AU - Karin Niepsch AU - Dirk Mueller AU - Richard Baum TI - <strong>Peptide Receptor Radionuclide Therapy (PRRT) in Patients with Progressive Grade 3 Neuroendocrine Neoplasms (NEN)</strong> DP - 2019 May 01 TA - Journal of Nuclear Medicine PG - 560--560 VI - 60 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/60/supplement_1/560.short 4100 - http://jnm.snmjournals.org/content/60/supplement_1/560.full SO - J Nucl Med2019 May 01; 60 AB - 560Objectives: Peptide receptor radionuclide therapy (PRRT), as treatment of grade 3 (G3) neuroendocrine neoplasms (NENs) with a Ki-67 proliferation index of &gt;20%, has been addressed only to a limited extent in literature. The aim of this study was to assess the safety and efficacy, in terms of survival analysis, of PRRT in patients who have SSTR expressing G3 NENs with a Ki-67 proliferation index of greater than 20%. The prognosis of patients with distinctly different Ki-67 proliferation indices and baseline 68Ga-SSTR and 18F-FDG PET/CT imaging was also evaluated. Methods: A total of 69 patients (41 males, 28 females; age 28-81 years) received PRRT with 177Lu and/or 90Y labeled DOTATATE or DOTATOC. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS), defined from start of PRRT, including a subgroup analysis for patients with a Ki-67 of &amp;#8804; 55% and &gt; 55%. Treatment response was evaluated according to RECIST 1.1 as well as by molecular imaging criteria (EORTC). Treatment-related adverse events were graded according to the CTCAE v.5.0. Results: PRRT was well-tolerated by all patients; no grade 3 or grade 4 hematotoxicity occurred and no clinically significant decline in renal function was observed. There was no hepatotoxicity. Forty-six patients had pancreatic NENs, 11 had unknown primary cancer, 6 had midgut NENs, 3 had gastric NENs, and 3 had rectal NENs. PRRT was applied as the first-line treatment in 8 patients (11.6%), as the second-line treatment in 25 patients (36.2%), and as the third line therapy in 28 patients (40.6%). The time span (mean ± SD) between biopsy for the assessment of Ki-67 and the first treatment cycle was 27.1 ± 36.8 months. Median follow-up was 94.3 months. The median PFS was 9.6 months and median OS was 19.9 months. For G3 NEN with a Ki-67 of more than 55% (n = 53), the median PFS was 11 months and median OS 22 months. Patients with a Ki-67 &gt;55% (n = 11), had a median PFS of 4 months and a median OS of 7 months. Of the 55 patients for whom a response assessment was performed, 86.0% (37/43) demonstrating an objective response had a SUVmax of greater than 15.0 on baseline 68Ga-SSTR PET. All 6 patients with an SUVmax of greater than 50 had an objective response to PRRT (4 PR and 2 SD). For patients with tumors of positive 68Gs-SSTR imaging, but no 18F-FDG uptake, the median PFS was 24 months and median OS was 42 months. A significant difference was found for both PFS and OS, with median PFS of 16 months and 5 months and median OS of 27 months and 9 months for an SUVmax of greater than 15.0 and an SUVmax of less than or equal to 15.0, respectively, on 68Ga-SSTR PET. In the group with 18F-FDG uptake scored as 3 or 4, the median PFS was 7.1 months and the median OS was 17.2 months. In the group with 18F-FDG uptake scored as 0-2, the median PFS was 24.3 months and the median OS was 41.6 months. Conclusion: PRRT was tolerated well, without significant adverse effects, and was efficacious in G3 NENs; the clinical outcome was promising, especially in patients with a Ki-67 index of less than or equal to 55% and even in patients for whom chemotherapy had failed. Baseline 18F-FDG along with SSTR molecular imaging was useful for stratifying G3 NEN patients with high uptake on 68Ga-SSTR PET/CT and no or minor 18F-FDG avidity - a mismatch pattern that was associated with a better long-term prognosis.