Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study

Abstract

Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21–54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3–4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.

P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms

“…Unadjusted HR (CI) and p-values are presented in Fig. 4, and were significant for p53 in the A and B comparison in the univariate analyses somatostatin receptor imaging as proposed in ENETS guidelines and in the study by Carlsen et al [16,33]. The present study also showed that the combination of SSTR-2a and p53 holds important prognostic information.…”

“…In contrast, surgery and chemotherapy, in particular adjuvant therapy, was associated by improved survival [1,16].…”

“…Patients with GEP-NEN with a Ki67-index > 20% diagnosed between the 1st of January 2012 and 31st of December 2016 and referred to the ENETS Neuroendocrine Tumour Centre of Excellence, Rigshospitalet were included. Patients with neuroendocrine cancer of unknown primary (CUP) predominantly with abdominal metastases were also included, in agreement with several prior publications [6,10,[15][16][17][18][19][20].…”

Theranostik von neuroendokrinen Tumoren

“…In einer retrospektiven, multizentrischen Auswertung von 114 Patienten mit G3neuroendokrinen Tumoren (hauptsächlich des Pankreas) betrug die Ansprechrate 42 % und das progressionsfreie Überleben 14 Monate. Ein höherer Ki-67-Index war mit einem kürzeren progressionsfreien Überleben verbunden [48]. Während diese Daten vielversprechend für die Anwendung von 177 Lu-DOTA-TATE bei G3-Tumoren sind, zeigte eine andere retrospektive Auswertung eine deutlich niedrigere Ansprechrate [49].…”

Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider

“…This concept is well established for treatment of neuroendocrine tumors (NETs) using peptide receptor radionuclide therapy (PRRT). This approach allows the targeted treatment of inoperable or metastatic NETs already proven in multiple clinical trials employing radiolabeled somatostatin analogs [2][3][4][5][6][7][8][9]. Based on the data received, the U.S. Food and Drug Administration (FDA) recently approved 177 Lu-labeled DOTA-TATE for PRRT treatment.…”