Table 2.
Clinical features of p-NENs in the present study according to the WHO 2017 and 2010 grading classification
| Factor | WHO 2017/2010 criteriaA | WHO 2017 criteriaA | WHO 2010 criteriaA | |||||
|---|---|---|---|---|---|---|---|---|
| NET G1 (N = 150) |
NET G2 (N = 158) |
NET G3 (N = 64) |
NEC G3 (N = 108) |
“NEC G3” (N = 172) |
All (N = 480) |
|||
| Gender | ||||||||
| Female | 88 (58.7%) | 97 (61.4%) | 38 (59.4%) | 62 (57.5%) | 100 (58.1%) | 285 (59.4%) | ||
| Age, yrs. | ||||||||
| Mean ± SD | 45.7 ± 15. | 49.1 ± 8.5 | 50.2 ± 7.8 | 54.1 ± 9.2 | 52.7 ± 10. | 49.5 ± 8.6 | ||
| Median | 2 | 48 | 52 | 57 | 253 | 50 | ||
| Range | 45 7–68 | 12–82 | 7–71 | 14–80 | 7–80 | 7–82 | ||
| Tumor size, cm. | 2.9 ± 2.1 | 5.5 ± 2.8 | 5.6 ± 3.5 | 5.9 ± 4.1 | 5.1 ± 3.9 | 5.6 ± 4.8 | ||
| Mean ± SD | 2.0 | 4.0 | 4.5 | 5.6 | 5.1 | 4.0 | ||
| Median Range | 0.3–7.2 | 1.2–14.5 | 1.8–7.6 | 1.6–13.1 | 1.6–13.1 | 0.3–14.5 | ||
| Functional status | ||||||||
| Non-functional | 62 (41.3%) | 88 (55.7%) | 44 (68.7%) | 72 (66.7%) | 116 (67.4%) | 266 (55.4%) | ||
| FunctionalB | 88 (58.7%) | 70 (44.3%) | 20 (31.3%) | 36 (33.3%) | 56 (32.6%) | 214 (44.6%) | ||
| Incidental diagnosis | 35 (23.3%) | 46 (29.1%) | 14 (21.9%) | 25 (23.1%) | 39 (22.7%) | 120 (25.0%) | ||
| Diagnosis after 2010 | 98 (65.3%) | 108 (68.4%) | 54 (84.4%) | 89 (82.4%) | 143 (83.1%) | 349 (72.7%) | ||
| Tumor location | ||||||||
| Body/tail | 85 (56.7%) | 100 (63.3%) | 43 (67.2%) | 68 (62.9%) | 111 (64.5%) | 296 (61.7%) | ||
| Surgical margin | ||||||||
| ″R0C | 126 (84.0%) | 124 (78.5%) | 33 (82.5%) | 46 (70.7%) | 89 (84.8%) | 339 (70.6%) | ||
| Postoperative medical therapyD | 31 (20.7%) | 41 (25.9%) | 29 (45.3%) | 61 (56.5%) | 90 (52.3%) | 162 (33.8%) | ||
| Vascular infiltration | 16 (10.7%) | 32 (20.3%) | 16 (25.0%) | 35 (32.4%) | 51 (29.7%) | 99 (45.3%) | ||
| Lymph involvement | 35 (23.3%) | 52 (32.9%) | 22 (34.4%) | 50 (46.3%) | 72 (41.9%) | 159 (33.1%) | ||
| Distant metastasisE | 20 (13.3%) | 30 (19.0%) | 12 (18.7%) | 32 (29.6%) | 44 (25.6%) | 94 (19.6%) | ||
| Hepatic | 12 (8.0%) | 15 (9.5%) | 6 (9.4%) | 20 (18.5%) | 26 (15.1%) | 51 (10.6%) | ||
| Bone | 5 (3.3%) | 8 (5.1%) | 3 (4.7%) | 10 (9.3%) | 13 (7.5%) | 26 (5.4%) | ||
| Lymph nodal | 10 (6.6%) | 14 (8.9%) | 4 (6.3%) | 16 (14.8%) | 20 (11.6%) | 44 (9.2%) | ||
| Out of contact | 30 (20.0%) | 38 (24.1%) | 9 (14.1%) | 23 (21.3%) | 32 (18.6%) | 100 (20.4%) | ||
| Dead at follow-up | 44 (36.7%) | 48 (40.0%) | 28 (50.9%) | 56 (69.1%) | 84 (60.0%) | 176 (46.3%) | ||
| 5-year OS | 75.8% | 58.4% | 35.1% | 11.1% | 21.2% | 53.0% | ||
| MST, mons. | 85.3 | 67.4 | 51.3 | 26.8 | 34.5 | 63.1 | ||
|
TNM staging system by AJCC 2017 8th staging manualF Stage I Stage II Stage III Stage IV |
WHO 2017 NET G1/G2/G3G (N = 372) | WHO 2017 NEC G3G (N = 108) | ||||||
| Cases(%) | Out of contact | Dead at follow-up | 5-year OS | Cases(%) | Out of contact | Dead at follow-up | 3-year OS | |
|
116 (31.2%) 108 (29.1%) 86 (23.1%) 62 (16.6%) |
16 (13.8%) 20 (18.5%) 20 (23.6%) 20 (32.3%) |
19 (19.0%) 23 (26.1%) 41 (62.1%) 37 (88.1%) |
89.2% 70.5% 51.2% 18.9% |
18 (16.7%) 30 (27.8%) 28 (25.9%) 32 (29.6%) |
6 (33.7%) 10 (33.3%) 2 (7.1%) 6 (18.8%) |
6 (50.0%) 13 (65.0%) 19 (73.1%) 18 (69.2%) |
80.8% 33.2% 7.1% NA |
|
A: The NET G1 and NET G2 were consistently defined in WHO 2017 and 2010 grading criteria for p-NENs, while the “NEC G3” of WHO 2010 criteria was composed of both NET G3 and NEC G3 of WHO 2017 criteria [8, 14]
B: Referring to insulinoma, gastrinoma, vasoactive intestinal polypeptidoma, adrenocorticotropic hormone adenoma, glucagonoma, pheochromocytoma, etc.
C: Referring to radical resections with both grossly and microscopically negative surgical margins
D: Referring to conventional chemotherapy and novel molecular targeted therapies
E: Distant metastases (hepatic, bone, lymph nodal) for patients with p-NENs was present at diagnosis
F: In the AJCC 2017 staging manual, one TNM system was originally proposed for G1/G2 p-NETs, the other for “G3 p-NECs” of WHO 2010 criteria
G: The G3 p-NETs of WHO 2017 grading classification were also staged by the system for G1/G2 p-NETs, while the G3 p-NECs of WHO 2017 criteria were staged by the system for pancreatic exocrine adenocarcinomas, as we have demonstrated in the previous report [19]
Abbreviations: p-NENs Pancreatic neuroendocrine neoplasms; WHO World Health Organization; NET Neuroendocrine tumors; NEC Neuroendocrine carcinoma; G Grading; TNM Tumor-node-metastasis; AJCC American Joint Committee On Cancer; NA Not applicable; OS Overall survival; MST Median survival time