TY - JOUR
T1 - Responses to Medical Treatment in 192 Patients with Pancreatic Neuroendocrine Neoplasms Referred to the Copenhagen Neuroendocrine Tumour Centre in 2000-2020
AU - Petersen, Sofie Skovlund
AU - Møller, Stine
AU - Slott, Cecilie
AU - Krogh, Jesper
AU - Hansen, Carsten Palnæs
AU - Kjaer, Andreas
AU - Holmager, Pernille
AU - Oturai, Peter
AU - Garbyal, Rajendra Singh
AU - Langer, Seppo W
AU - Knigge, Ulrich
AU - Andreassen, Mikkel
PY - 2024/3/18
Y1 - 2024/3/18
N2 - BACKGROUND: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence.AIM: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN.METHODS: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192).RESULTS: Median OS was 36 (95% CI: 26-46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9-9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1-7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%).CONCLUSION: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide.
AB - BACKGROUND: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence.AIM: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN.METHODS: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192).RESULTS: Median OS was 36 (95% CI: 26-46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9-9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1-7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%).CONCLUSION: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide.
KW - chemotherapy
KW - everolimus
KW - pancreatic neuroendocrine tumors
KW - peptide receptor radionuclide therapy
KW - somatostatin analogue
KW - treatment efficacy
UR - http://www.scopus.com/inward/record.url?scp=85188688818&partnerID=8YFLogxK
U2 - 10.3390/cancers16061190
DO - 10.3390/cancers16061190
M3 - Comment/debate
C2 - 38539524
SN - 2072-6694
VL - 16
JO - Cancers
JF - Cancers
IS - 6
M1 - 1190
ER -