Factors predicting outcome of G1/2 GEP NET after PRRT with Lu177-octreotate.

Abstract

e14565 Background: Outcome analyses of G1/2 NEN stage IV after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. This study aims to establish predictors of survival. Methods: Retrospective analysis of 74 consecutive GEP NET patients undergoing PRRT with 177Lu-octreotate. Patients had unresectable metastatic disease and a G1/2 grading (33 pancreatic, 41 non-pancreatic GEP- NET), documented morphologic or clinical progression within < 12 months and/or uncontrolled disease. Response (modified SWOG criteria) was correlated with potential impact factors: origin, function, burden, and uptake of tumor, age, Ki-67-index, Karnofsky score, baseline tumor marker levels. Predictors for survival were analyzed with Kaplan-Meier curves (log-rank test) and multivariate analysis (p<0.05). Results: The response rates were 36.5% PR, 17.6% MR, 35.1% SD, and 10.8% PD for the entire cohort, 54.5% PR, 18.2% MR, 18.2% SD, and 9.1% PD for pancreatic NET, and 22.0% PR, 17.1% MR, 48.8% SD, and 12.2% PD for non-pancreatic GEP-NET. The median progression-free (PFS) and overall (OS) survival was 26 months (95% CI, 18.3 - 33.7) and 55 months (95% CI, 48.8–61.2), respectively. The only factor associated with decreased PFS was a Ki-67 index >10% (p=0.002). For OS, besides the Ki-67 index, a Karnofsky score ≤70% and a baseline NSE of >15 ng/ml independently predicted shorter survival (each p<0.005, HR 3.0 - 3.4). Patients with a Ki-67 index >10% still had a median PFS and OS of 19 and 34 months, respectively. Conclusions: This study confirms the favorable outcome of G1/2 NET after PRRT. Independent predictors of survival are the Ki-67 index, the patient‘s performance status and the baseline NSE level. Nevertheless, patients with a Ki-67 >10% may still benefit from PRRT as demonstrated by the long-term outcome.

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

“… Pathology: tumours with low Ki-67 or low-grade are usually associated with higher expression of SSTR, a more indolent disease course and poorer responses to chemotherapy, in comparison with tumours with high Ki-67 or higher-grade [ 117 ]. Low Ki-67 seems to be an independent predictor of better response to PRRT [ 118 ], although the observed benefit was present in both G1 (HR 0.24 (95%-CI 0.13–0.44)) and G2 (HR 0.15 (95%-CI 0.07–0.34)) patients with midgut NETs [ 36 ]. Similarly, the benefit from lanreotide was comparable in both groups of patients [G1 (HR 0.43 (95%-CI 0.25–0.74)) vs. G2 (Ki-67 up to 10%) (HR 0.45 (95%-CI 0.22–0.91)].…”