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Multicenter Study
. 2025 Aug;133(3):316-324.
doi: 10.1038/s41416-025-03054-w. Epub 2025 May 17.

Characteristics and treatment outcome in a prospective cohort of 639 advanced high-grade digestive neuroendocrine neoplasms (NET G3 and NEC). The NORDIC NEC 2 study

Halfdan Sorbye  1   2 , Geir Olav Hjortland  3 , Lene Weber Vestermark  4 , Morten Ladekarl  5   6 , Johanna Svensson  7 , Anna Sundlöv  8 , Eva Tiensuu Janson  9 , Herish Garresori  10 , Eva Hofsli  11 , Christian Kersten  12 , Hege Elvebakken  13 , Per Pfeiffer  14 , Siren Morken  15   16 , Jorg Assmus  17 , Inger Marie Bowitz Lothe  18 , Elizaveta Tabaksblat  5 , Ulrich Knigge  19 , Anne Couvelard  20 , Aurel Perren  21 , Seppo W Langer  22   23
Affiliations
Multicenter Study

Characteristics and treatment outcome in a prospective cohort of 639 advanced high-grade digestive neuroendocrine neoplasms (NET G3 and NEC). The NORDIC NEC 2 study

Halfdan Sorbye et al. Br J Cancer. 2025 Aug.

Erratum in

Abstract

Background: Digestive high-grade neuroendocrine neoplasms (HG-NEN) are rare and classified as neuroendocrine carcinomas (NEC) or neuroendocrine tumours G3 (NET G3), and differ in clinical and molecular characteristics, response to treatment and prognosis.

Methods: Prospective multicenter study registering clinical data on patients with digestive HG-NEN. Treatment outcome in patients with advanced disease was compared after centralized pathological re-evaluation.

Results: 427 NEC and 117 NET G3 received palliative chemotherapy. Immediate progression rate was 41% and 24%, progression-free survival (PFS) 3.4 m and 7.4 m, overall survival (OS) 7.4 m and 21.8 m for NEC and NET G3, respectively. Significant factors for OS in NEC were performance status (PS), Ki-67 > 55%, alkaline phosphatase (ALP), age, sex and for PFS colorectal primary and PS. NEC Ki-67 < 55% had similar OS comparing treatment. Significant factors for OS in NET G3 were platinum-based treatment, PS, age and ALP, and for PFS platinum-based treatment.

Conclusions: Survival was shorter than expected in this unique population-based cohort of advanced digestive HG-NEN, likely due to inclusion of elderly and patients with poor PS. Several novel prognostic factors were identified for NEC and NET G3. An initial sub-effective platinum-based treatment for NET G3 could not be compensated by later-line treatment.

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Conflict of interest statement

Competing interests: ML achieved an unrestricted grant from Scandion Oncology, Denmark. All other authors have declared no conflicts of interest. Ethics approval and consent to participate: The study was conducted according to the Declaration of Helsinki and approved by ethics committees in Norway (REK-vest-2012/940), Sweden (REC-Uppsala-Dnr-2012/285) and Denmark (Region-Hovedstaden-H-4-2012-108). All patients signed written informed consent.

Figures

Fig. 1
Fig. 1. Progression-free survival and overall survival in NET G3 and NEC.
Progression-free survival (PFS) (a) and overall survival (OS) (b) in NET G3 and NEC patients given first-line chemotherapy and OS according to Ki-67 index in NET G3 (c) and NEC (d).
Fig. 2
Fig. 2. Overall survival in NEC.
Overall survival (OS) in NEC patients given first-line chemotherapy according to (a) performance status, (b) first-line chemotherapy regimen when Ki-67 < 55% and (c) alkaline phosphatase (ALP) level.
Fig. 3
Fig. 3. Progression-free survival and overall survival in NET G3.
Overall survival (OS) (a) and progression-free survival (PFS) (b) in NET G3 with Ki-67 < 55% according to first-line chemotherapy regimen and OS in NET G3 according to performance status (c) and alkaline phosphatase (ALP) level (d).
See this image and copyright information in PMC

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