Radiolabeled somatostatin analogues therapy in advanced neuroendocrine tumors: a single centre experience

Abstract

The aim of this study was to assess the efficacy of PRRT in patients with advanced neuroendocrine tumors (NETs). Patients and Methods. From January 2007 to August 2011, we enrolled 65 patients (m/f 38/27; mean age 65 years, range 33-83) with advanced NETs having enhanced SSTR expression, treated with PRRT. The enhanced expression of SSTR was assessed using (68)Ga-DOTATOC/DOTATATE PET/CT. Among all the enrolled patients, 6 of them were excluded from the present analysis since they voluntarily interrupted treatment. Mean activity/cycle of 2.6 GBq ((90)Y-DOTATOC/DOTATATE) or 6.0 GBq ((177)Lu-DOTATOC/DOTATATE) was administrated intravenously (max 9 cycles). Results. Complete response (CR) was found in 1/59 (2%) patients, partial remission (PR) in 24/59 (40.5%) patients, stable disease (SD) in 24/59 (40.5%), and progression (PD) in 10/59 (17%) patients. The overall tumor response rate (CR + PR) was 42.5%. In 40.5% of patients, the disease could be stabilized. Overall, 49 out of 59 patients had no tumor progression (83%). Twelve patients out of 59 (20%) had grade 2-3 hematological side effects including anemia, thrombocytopenia, and leukopenia. Long-term nephrotoxicity was observed in 3 patients (2 moderate, 1 severe). Conclusions. PRRT is a promising perspective for patients with advanced NETs.

Figure 1

⁶⁸Ga-DOTATOC PET/CT: liver, lung, lymph node, and bone metastases from NET of unknown origin.

Figure 2

Male, 56 years old, with pancreatic NET and multiple liver metastases. ⁶⁸Ga-DOTATOC PET/CT before therapy (a) and after PRRT (b). The result was a partial response.

Figure 3

Male, 73 year old, pancreas NET with liver metastases. ⁶⁸Ga-DOTATOC PET/CT before (left) and after therapy (right). PRRT with ⁹⁰Y-DOTATOC (2 cycles) and ¹⁷⁷Lu-DOTATOC (4 cycles) was administered at interval of 2 months. The response was complete in the liver but partial in the pancreatics region (arrow).

Figure 4

(a) Mann-Whitney test plot shows a significant difference in cumulated administered activity between PD and non-PD patients (P < 0.001). Similar results (b) have been obtained by using Mann-Whitney test excluding patients who had SD and thus considering only patients who had objective response (P = 0.002). When all subgroups of patients are considered (c), the cumulated administered activity remains significantly different in PD group versus both objective response and SD groups while no significant differences have been found in cumulated administered activity comparing patients who presented objective response and stable disease (P = 0.435). PD = patients who presented progressive disease; non-PD = patients who presented complete or partial response or disease stabilization; objective response = patients who presented complete or partial response; SD = patients who presented stable disease.