Well-Differentiated Grade 3 Neuroendocrine Tumors

Abstract

Objectives:We evaluated a population-based cohort of metastatic welldifferentiated grade 3 gastroenteropancreatic neuroendocrine tumors (G3 NETs) to describe their characteristics, prognosis, and treatment outcomes. Methods:The British Columbia provincial database was queried for G3 NETs diagnosed 2004 to 2021, and charts were reviewed to describe clinical features and outcomes.Results: Forty-one patients were identified, most were diagnosed with pancreatic (58.5%) or midgut (26.8%) primary tumor and Ki-67 was less than 55% in 68.3%. The primary was resected in 19 (46.3%) with median disease-free survival of 25.2 months. Once metastatic, patients received a median of one line of systemic therapy. Median overall survival with metastatic disease was 33.8 months. Median progression-free survival was longest in patients treated with capecitabine-temozolomide (20.6 months) or somatostatin analogs (7.9 months), while etoposide-platinum provided little benefit (2.4 months). Limited data of efficacy for targeted therapies and radionuclide therapy was available. Seven patients (17.1%) were also treated with local therapies, which were associated with improved overall survival (median not reached, hazard ratio, 0.23; P = 0.012).Conclusions: Capecitabine-temozolomide and somatostatin analogs were associated with clinically meaningful benefit, and use of local therapies provided benefits in selected patients. Multidisciplinary discussion is essential to optimize individual outcomes in this heterogeneous population.

A systematic review of therapeutic strategies in gastroenteropancreatic grade 3 neuroendocrine tumors

“…In all, 29 studies met the predefined inclusion criteria, totaling 2955 NET patients, of which 25.8% (761 patients; range: 5–74) had G3 GEP or unknown primary G3 NET origins. 4 , 12 – 39…”

“…Pathology review was performed in 23 studies (79.3%). 10 , 12 – 14 , 16 , 18 , 20 – 27 , 29 , 31 – 36 , 38 , 39 As shown in Table 3 , the Ki-67 index was described in 15 studies, and the median values ranged from 23% to 61%; p53 immunohistochemistry (IHC) expression and/or TP53 mutation status was evaluated in six studies, with mutation or hyperexpression present in 0% to 21%; DAXX/ATRX and MEN1 mutation status were described in three studies, and were found in 0–25% and 0–21% of the patients, respectively, mostly in pancreatic NET.…”

“… 13 – 15 , 19 , 21 , 22 , 25 , 26 , 28 , 29 , 32 , 33 , 38 In all, 14 studies did not describe disease response assessment methodology. 12 , 16 – 18 , 23 , 24 , 27 , 31 – 37 , 39…”

“…In all, 14 studies (48.3%) included only patients with metastatic disease, 10 , 15 , 19 – 21 , 25 – 30 , 33 , 35 , 39 six studies reported only patients with localized disease (20.7%), 16 , 17 , 23 , 24 , 31 , 34 and nine contained both (31%). 12 – 14 , 18 , 22 , 32 , 36 – 38 …”

“…In all, 17 studies described palliative treatments used in the first, second, or later lines. 12 – 15 , 19 – 21 , 25 , 26 , 28 – 30 , 33 , 35 , 37 – 39 The regimens used were platin doublets or triplets, capecitabine and temozolomide (CAPTEM), folinic acid + fluorouracil + oxaliplatin (FOLFOX), and somatostatin analog (SSA), among others. Table 5 summarizes the outcomes of systemic chemotherapies, respective Ki-67 indices, and lines of treatment.…”