TY - JOUR
T1 - 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
T2 - Clinical Studies
AU - Sorbye, Halfdan
AU - Hjortland, Geir Olav
AU - Vestermark, Lene Weber
AU - Ladekarl, Morten
AU - Svensson, Johanna
AU - Sundlöv, Anna
AU - Janson, Eva Tiensuu
AU - Garresori, Herish
AU - Hofsli, Eva
AU - Kersten, Christian
AU - Elvebakken, Hege
AU - Pfeiffer, Per
AU - Morken, Siren
AU - Assmus, Jorg
AU - Lothe, Inger Marie Bowitz
AU - Tabaksblat, Elizaveta
AU - Knigge, Ulrich
AU - Couvelard, Anne
AU - Perren, Aurel
AU - Langer, Seppo W.
PY - 2025
Y1 - 2025
N2 - 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. (Figure presented.)
AB - 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. (Figure presented.)
U2 - 10.1038/s41416-025-03054-w
DO - 10.1038/s41416-025-03054-w
M3 - Journal article
AN - SCOPUS:105005119839
SN - 0007-0920
JO - British Journal of Cancer
JF - British Journal of Cancer
M1 - e13249
ER -