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

Esben Andreas Carlsen; Nicola Fazio; Dan Granberg; Simona Grozinsky-Glasberg; Hojjat Ahmadzadehfar; Chiara Maria Grana; Wouter T. Zandee; Jaroslaw Cwikla; Martin A. Walter; Peter Sandor Oturai; Anja Rinke; Andrew Weaver; Andrea Frilling; Sara Gritti; Anne Kirstine Arveschoug; Amichay Meirovitz; Ulrich Knigge; Halfdan Sorbye

doi:10.1530/erc-18-0424

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

Esben Andreas Carlsen, Nicola Fazio, Dan Granberg, Simona Grozinsky-Glasberg, Hojjat Ahmadzadehfar, Chiara Maria Grana, Wouter T. Zandee, Jaroslaw Cwikla, Martin A. Walter, Peter Sandor Oturai, Anja Rinke, Andrew Weaver, Andrea Frilling, Sara Gritti, Anne Kirstine Arveschoug, Amichay Meirovitz, Ulrich Knigge, Halfdan Sorbye

35 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Endocrine-Related Cancer
Vol/bind	26
Udgave nummer	2
Sider (fra-til)	227-239
ISSN	1351-0088
DOI	https://doi.org/10.1530/erc-18-0424
Status	Udgivet - feb. 2019

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10.1530/erc-18-0424

ERC-18-0424.pdfForlagets udgivne version, 1,46 MB

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Carlsen, E. A., Fazio, N., Granberg, D., Grozinsky-Glasberg, S., Ahmadzadehfar, H., Grana, C. M., Zandee, W. T., Cwikla, J., Walter, M. A., Oturai, P. S., Rinke, A., Weaver, A., Frilling, A., Gritti, S., Arveschoug, A. K., Meirovitz, A., Knigge, U., & Sorbye, H. (2019). Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study. Endocrine-Related Cancer, 26(2), 227-239. https://doi.org/10.1530/erc-18-0424

Carlsen, EA, Fazio, N, Granberg, D, Grozinsky-Glasberg, S, Ahmadzadehfar, H, Grana, CM, Zandee, WT, Cwikla, J, Walter, MA, Oturai, PS, Rinke, A, Weaver, A, Frilling, A, Gritti, S, Arveschoug, AK, Meirovitz, A, Knigge, U & Sorbye, H 2019, 'Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study', Endocrine-Related Cancer, bind 26, nr. 2, s. 227-239. https://doi.org/10.1530/erc-18-0424

@article{38a6b39f1ae34a3c875f22d0edb456b9,

title = "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.",

keywords = "neuroendocrine tumors, neuroendocrine carcinoma, neuroendocrine neoplasm, high-grade, peptide receptor radionuclide therapy, radiolabeled somatostatin analogues, (177)Lutetium, (90)Yttrium, progression-free survival, overall survival",

author = "Carlsen, {Esben Andreas} and Nicola Fazio and Dan Granberg and Simona Grozinsky-Glasberg and Hojjat Ahmadzadehfar and Grana, {Chiara Maria} and Zandee, {Wouter T.} and Jaroslaw Cwikla and Walter, {Martin A.} and Oturai, {Peter Sandor} and Anja Rinke and Andrew Weaver and Andrea Frilling and Sara Gritti and Arveschoug, {Anne Kirstine} and Amichay Meirovitz and Ulrich Knigge and Halfdan Sorbye",

year = "2019",

month = feb,

doi = "10.1530/erc-18-0424",

language = "English",

volume = "26",

pages = "227--239",

journal = "Endocrine - Related Cancer",

issn = "1351-0088",

publisher = "BioScientifica Ltd.",

number = "2",

}

TY - JOUR

T1 - Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3

T2 - a multicenter cohort study

AU - Carlsen, Esben Andreas

AU - Fazio, Nicola

AU - Granberg, Dan

AU - Grozinsky-Glasberg, Simona

AU - Ahmadzadehfar, Hojjat

AU - Grana, Chiara Maria

AU - Zandee, Wouter T.

AU - Cwikla, Jaroslaw

AU - Walter, Martin A.

AU - Oturai, Peter Sandor

AU - Rinke, Anja

AU - Weaver, Andrew

AU - Frilling, Andrea

AU - Gritti, Sara

AU - Arveschoug, Anne Kirstine

AU - Meirovitz, Amichay

AU - Knigge, Ulrich

AU - Sorbye, Halfdan

PY - 2019/2

Y1 - 2019/2

N2 - 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.

AB - 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.

KW - neuroendocrine tumors

KW - neuroendocrine carcinoma

KW - neuroendocrine neoplasm

KW - high-grade

KW - peptide receptor radionuclide therapy

KW - radiolabeled somatostatin analogues

KW - (177)Lutetium

KW - (90)Yttrium

KW - progression-free survival

KW - overall survival

U2 - 10.1530/erc-18-0424

DO - 10.1530/erc-18-0424

M3 - Journal article

C2 - 30540557

SN - 1351-0088

VL - 26

SP - 227

EP - 239

JO - Endocrine - Related Cancer

JF - Endocrine - Related Cancer

IS - 2

ER -

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

Abstract

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