Predictors of Long-Term Outcome in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors After Peptide Receptor Radionuclide Therapy with ¹⁷⁷Lu-Octreotate

Abstract

Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. Using a single-center analysis, we aimed to establish predictors of survival. Methods: We retrospectively analyzed a consecutive cohort of 74 patients who had metastatic GEP NET and underwent PRRT with 177 Lu-octreotate (mean activity of 7.9 GBq per cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33 with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or clinical progression within less than 12 mo or uncontrolled disease under somatostatin analog treatment. Responses were evaluated according to modified Southwest Oncology Group criteria. Potential predictors of survival were analyzed with the Kaplan-Meier curve method (log-rank test) and multivariate analysis (P , 0.05). Results: The response rates were 36.5% partial response, 17.6% minor response, 35.1% stable disease, and 10.8% progressive disease for the entire cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and 9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1% minor response, 48.8% stable disease, and 12.2% progressive disease for nonpancreatic GEP NET. The median progression-free survival and overall survival were 26 mo (95% confidence interval, 18.3-33.7) and 55 mo (95% confidence interval, 48.8-61.2), respectively. Besides the Ki-67 index, a Karnofsky performance score of less than or equal to 70%, a hepatic tumor burden of greater than or equal to 25%, and a baseline plasma level of neuron-specific enolase of greater than 15 ng/mL independently predicted shorter overall survival (hazard ratio, 2.1-3.1). Patients with a Ki-67 index of greater than 10% still had median progression-free survival and overall survival of 19 and 34 mo, respectively. Conclusion:The results of this study demonstrated the favorable response and long-term outcome of patients with G1/G2 GEP NET after PRRT. Independent predictors of survival were the Ki-67 index, the patient's performance status (Karnofsky performance scale score), the tumor burden, and the baseline neuron-specific enolase level. Even patients with a Ki-67 index of greater than 10% seemed to benefit from PRRT, with a good response and a notable long-term outcome. We present the first evidence, to our knowledge, that even in patients with metastatic disease the distinction between G1 and G2-in particular, between G1 (Ki-67 index of 1%-2%) and low-range G2 (Ki-67 index of 3%-10%)-provides prognostic stratification. Pept ide receptor radionuclide therapy (PRRT) is a highly efficient modality for the systemic treatment of gastroenteropancreatic neuroendocrine tumors (GEP NET) (1-4). The compound [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate) is frequently used for this purpose. Outstanding response and survival data are ava...

Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy

“…In contrast to previous findings, hepatic tumor burden did not turn out as an independent survival predictor, mainly since almost the entire cohort of our patients (97 %) suffered from liver metastases [48]. Of note, Ki67 did not correlate significantly with the investigated heterogeneity parameters emphasizing their independence.…”

Prognostic Stratification of Metastatic Gastroenteropancreatic Neuroendocrine Neoplasms by 18F-FDG PET: Feasibility of a Metabolic Grading System

“…There are 2 reports proposing the baseline plasma NSE level as a potential risk factor for survival in patients with metastatic NENs (9,28). There is no well-established explanation for this phenomenon, but an inverse relation between tumor differentiation and plasma NSE levels in NENs was reported earlier (29) and substantiated in a recent larger study (30).…”

“…Although the differentiation of G1 from G2 helps to predict the tendency of the tumor to metastasize, the differentiation of G1-G2 from G3 profoundly guides treatment of metastatic patients-for example, implementation of first-line chemotherapy versus less aggressive treatment such as somatostatin analogs (4)(5)(6). Response to treatment may be homogeneous within the entire G1-G2 range (7), but outcome of uniformly treated metastatic NENs is still influenced by the proliferation index, even within the G1-G2 range (8,9).…”

Somatostatin Receptor–Targeted Radiopeptide Therapy with 90Y-DOTATOC and 177Lu-DOTATOC in Progressive Meningioma: Long-Term Results of a Phase II Clinical Trial

“…Somatostatin-based radiopeptide therapy with 90 Y-DOTATOC and 177 Lu-DOTATOC has an established value for treating patients with neuroendocrine tumors (17,(19)(20)(21). On the basis of the current results, DOTATOC is a relatively safe treatment option that should be considered for patients with progressive nonoperable meningiomas who have failed all other treatment options.…”