Introduction
Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of neoplasms that show variable behavior, from indolent to aggressive. The clinical behavior is mainly related to the grade of the disease. In recent years, the incidence of such neoplasms has increased markedly, in part due to incidental findings of small low-grade lesions (either G1 or G2), both of which are often treated conservatively.
Aims & Methods
Aim of the study was to explore the biological and clinical heterogeneity of grade 2 (G2) PanNENs to better define clinical features, prognosis, and therapeutic options.
This is an observational, retrospective, single-center study examining patients with confirmed G2 PanNENs from January 2005 to December 2022. Demographic, clinical, biochemical, histopathological, imaging, and therapeutic data were collected for each included patient. Overall survival (OS) and progression-free survival (PFS) from diagnosis were also evaluated and compared with the G1 PanNENs group.
Results
A total of 51 PanNENs were collected: 29 were G1, 20 were G2, and 2 were G3. Among the G2 PanNENs, 12 patients (60%) were female and the median age at diagnosis was 56.5 years [IQR, interquartile range from 50.25 to 70.5]. Five patients were at stage I at diagnosis, 3 at stage II, 2 at stage III, and 10 at stage IV; 5 patients (25%) had a functioning PanNEN. The median Ki67% at diagnosis was 5% [IQR 4-12]; the median size of the primary tumor was 30 mm [IQR 16-43]. Fifteen patients (75%) underwent surgery, 13 as 1st-line therapy, and 2 as 2nd-line. Pancreaticoduodenectomy and distal splenopancreatectomy were equally the most frequently performed types of surgery (both 30.7%). Of the 15 surgical patients, an R0 outcome was achieved in 9 (60%) and 8 (53.3%) other patients underwent further therapies: 7 patients received somatostatin analogs (SSAs), 3 peptide receptor radionuclide therapy (PRRT), 2 targeted therapy, and 1 chemotherapy. Of the other nonsurgical patients, one received first-line systemic treatment (4 SSAs and 1 PRRT). The median PFS of G2 PanNENs after 1st-line treatment was significantly different from that of G1 PanNENs (25.5 months vs undefined, p <0.0001). The median OS of G2 PanNENs was shorter compared to G1 PanNENs, but did not reach statistical significance (83 vs 87 months, p=n.s.). When comparing demographic, clinical, biochemical, histopathological, and therapeutic data between G2 and G1 PanNENs, no variables other than disease stage at diagnosis (p=0003) were significantly different.
| Demographic, clinical, biochemical, histopathological, and prognostic data on G2 and G1 pancreatic neuroendocrine neoplasms. |
| G2
(20 patients)
| G1
(29 patients)
| p value
|
Neoplasm diameter (median, mm)
| 30 [IQR 16-43]
| 15.5 [IQR 11.3-37.3]
| 0.92
|
Ki67 (%)
| 5 [4-12]
| 1 [IQR 1-2]
| 0.25
|
Stage at diagnosis (n of patients)
| Stage I 5
Stage II 3
Stage III 2
Stage IV 10
| Stage I 14
Stage II 8
Stage III 3
Stage IV 0
| 0.0003
|
Surgery as 1st-line therapy (yes, %)
| 15 (51.7%)
| 12 (41.4%)
| 0.12
|
Median PFS (months)
| 25.5
| Not reached
| <0.0001
|
Median OS (months)
| 83
| 87
| n.s.
|
Conclusion
This study found that surgery was a common treatment option for G2 PanNENs. However, while the majority of surgical patients achieved R0 results, a significant proportion had to undergo further therapies due to disease progression. The prognosis of G2 PanNENs was significantly worse than that of G1 in terms of both PFS and OS, although the median OS was not statistically different. The disease stage was more advanced in G2 PanNENs than in G1 PanNENs. Overall, these findings suggest that G2 PanNENs deserve a different personalized treatment approach than G1 PanNENs and that further research is needed to better understand the factors affecting their prognosis.
