Survival outcomes for patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with lutetium-177-dotatate (Lu-177) in a Brazilian reference center: A six-year follow-up experience.
Authors: Souza Zenaide Silva , Xavier Camila Bragança , Mendes Gomes Siqueira Luciana Beatriz , Barbosa de Medeiros Maria Fernanda , de Souza Micelange Carvalho , Begnami Maria Dirlei de Souza , Pereira Allan Andresson Lima , Marin José Flávio Gomes , Buchpiguel Carlos Alberto , Costa Frederico 
Published: January 2023

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Background: GEP-NETs are the most common NETs primary site. Lu-177 is the standard treatment for patients with grade 1 (G1) or grade 2 (G2) midgut NETs who had disease progression during first-line somatostatin analog therapy. Methods: We performed a retrospective chart review including advanced GEP-NETs treated with at least one Lu-177 dose from our institution. Overall survival (OS) and progression-free survival (PFS) were calculated from the first Lu-177 dose using the Kaplan–Meier method. Cox regression analysis was performed for PFS adjusted by grade, primary tumor site, metastasis sites (1 vs.≥ 2), presence of liver metastasis, and previous local or other systemic treatments. Krenning Score (KS) and the maximum standardized uptake value (SUVmax) were calculated from the pre-treatment Ga-68 PET/CT. Maximally Selected Rank Statistics (MSRS) test was used for SUVmax simple cutpoint estimate and PFS was calculated using the Kaplan–Meier method. Results: 36 pts were included; the median age was 51 (range: 33-80). 19 (52.8%) pts had primary pancreatic NET and 17 (47.2%) had non-pancreatic primary NETs. Tumor grading was classified based on Ki67%. 10 pts were G1 (28.6%), 18 pts were G2 (51.4%), 7 pts were G3 (20%). 7 pts (19.4%) and 28 pts (77.7%) had KS 3 and 4, respectively. 125 cycles of Lu-177 were applied with 3.5 cycles per pts (mean; range: 1-6). 12 (33.3%) pts experienced grade 1 and 2 toxicity, mainly fatigue (n=4). No grade 3 or 4 toxicities were reported. 4 (11.1%) patients died (n=3 G3; n=1 G2) with median follow-up of 90.5 months (range: 16-122). 11 pts (30.6%) lost follow-up after Lu-177 treatment. 29 pts (80.5%) were eligible for OS. 24-month and 36-month survival rates were 92,7% (95% CI 73.7 - 98.1) and 86,9% (95% CI 63.5 - 95.7) respectively. The median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 tumors (p=0.001). 34 (94%) pts were eligible for PFS. The median PFS was 23 months (95% CI 30.5-64.9) for the entire cohort. The median PFS was 30 months for G1, 27 months for G2 pts, and 7 months for G3 pts. G1/G2 vs. G3 median PFS was statistically different in the uni- and multivariate analysis [HR 8.41 (95%CI 2.2-31.0; p=0.001)]. The primary site, metastasis sites, number of previous systemic treatments, previous local treatment, and presence of liver metastasis did not correlate with PFS in the multivariate analyses. Pts with SUVmax > 34.53 exhibited a statistical trend toward a longer PFS (median 52.0 vs 18.7 months; p=0.06). Conclusions: This real-life study supports that Lu-177 provides long-term PFS in pts KS 3/4 with G1/G2 GEP-NETs independent of clinical characteristics and primary site. Although G3 pts have worse survival, selected G3 GEP-NETs may experience long OS after Lu-177 treatment. SUVmax values from the pre-treatment Ga-68 PET/CT study may select ideal pts for Lu-177.