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

in Endocrine-Related Cancer
Correspondence should be addressed to E A Carlsen: esben.a.carlsen@gmail.com
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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.

 

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    An example of PRRT in GEP NEN G3. Left-hand side: fused positron emission tomography (PET) and computer tomography (CT), transverse plane at kidney level. Right-hand side: whole-body maximum intensity projection, PET. A 47-year-old female with high-grade pancreatic neuroendocrine neoplasm (Ki67 of 70%), metastatic to the liver. Received three cycles of peptide receptor radionuclide therapy with 177Lu-DOTATATE. Follow-up with a durable partial response. PRRT, petide receptor radionuclide therapy; m, months. A full colour version of this figure is available at https://doi.org/10.1530/ERC-18-0424.

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    Kaplan-Meier curves of PFS for 149 patients with GEP NEN G3 treated with PRRT. Stratification by Ki-67 index (n = 148), differentiation (n = 122), performance status (PS) (n = 126), combined Ki-67 index and differentiation (n = 119), LDH (n = 111) and ALP (n = 121), respectively. PFS, progression free-survival; GEP NEN G3, gastroenteropancreatic neuroendocrine neoplasm grade 3; PRRT, peptide receptor radionuclide therapy. A full colour version of this figure is available at https://doi.org/10.1530/ERC-18-0424.

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    Kaplan-Meier analysis of OS for 149 patients with GEP NEN G3 treated with PRRT. Stratification by Ki-67 index (n = 148), differentiation (n = 122), performance status (PS) (n = 126), combined Ki-67 index and differentiation (n = 119), LDH (n = 111) and ALP (n = 121), respectively. OS, overall survival; GEP NEN G3, gastroenteropancreatic neuroendocrine neoplasm grade 3; PRRT, peptide receptor radionuclide therapy. A full colour version of this figure is available at https://doi.org/10.1530/ERC-18-0424.

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