| 1. |
- Jensen, Robert T., et al.
(author)
-
Unmet Needs in Functional and Nonfunctional pancreatic neuroendocrine neoplasms
- 2019
-
In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 26-36
-
Journal article (peer-reviewed)abstract
- Recently, the European Neuroendocrine Tumor Society (ENETS) held working sessions composed of members of the advisory board and other neuroendocrine neoplasm (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This report briefly summarizes the main proposed areas of unmet needs in patients with functional and nonfunctional pancreatic NENs.
|
|
| 2. |
- Sorbye, Halfdan, et al.
(author)
-
Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)
- 2019
-
In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 54-62
-
Journal article (peer-reviewed)abstract
- Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Ali, Abir Salwa, 1986-, et al.
(author)
-
Candidate protein biomarkers in pancreatic neuroendocrine neoplasms grade 3
- 2020
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumours that compose 1-2% of all pancreatic tumours. Patients with metastatic grade 3 neoplasia are usually treated with chemotherapy but have a poor progression-free and overall survival. According to the WHO 2017 classification, they are divided into neuroendocrine tumours (NETs) G3 and neuroendocrine carcinomas (NECs). Despite the new classification, new diagnostic and prognostic biomarkers are needed to sub-categorise the patients and to help guide therapy decisions. Blood from 42 patients and 42 healthy controls were screened for the presence of 92 proteins with the Immuno-Oncology panel using the Proximity Extension Assay provided by Olink Biosciences. Immunohistochemical staining of FAS ligand (FASLG) was performed on 16 patient tumour specimens using a commercial antibody. Fifty-four out of 87 evaluable proteins differed significantly in concentration between blood from patients and blood from healthy controls. FASLG was the only protein for which the concentration in blood was significantly lower in patients compared to controls and the levels correlated negatively to Ki-67 index. Seven of 14 evaluable PanNEN G3 specimens showed FASLG immunoreactivity in the tumour cells while there was scattered immunoreactivity in immune cells. Positive FASLG immunoreactivity correlated to well-differentiated morphology. FASLG concentration in blood was significantly lower in patients with pancreatic NENs G3 compared to controls, and the expression in tumour tissue was variable. Furthermore, FASLG was negatively correlated to Ki-67 and was more frequently expressed in well-differentiated tumours. Taken together, these results may suggest a role of FASLG in PanNENs.
|
|
| 6. |
- Ali, Abir Salwa, et al.
(author)
-
Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma
- 2017
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
-
Journal article (peer-reviewed)abstract
- Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. Conclusion In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.
|
|
| 7. |
- Ali, Abir Salwa, et al.
(author)
-
Intravenous versus oral etoposide : efficacy and correlation to clinical outcome in patients with high-grade metastatic gastroenteropancreatic neuroendocrine neoplasms (WHO G3)
- 2018
-
In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 35:4
-
Journal article (peer-reviewed)abstract
- High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter-and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (= 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan-Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.
|
|
| 8. |
- Ali, Abir Salwa, 1986-, et al.
(author)
-
PD-L1 expression in gastroenteropancreatic neuroendocrine neoplasms grade 3
- 2020
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12
-
Journal article (peer-reviewed)abstract
- Gastroenteropancreatic neuroendocrine neoplasms grade 3 (GEP-NENs G3) are rare tumors. These highly aggressive neoplasms are traditionally treated with platinum-based chemotherapy in combination with etoposide. Immune checkpoint proteins such as programmed cell death ligand (PD-L1) may have a role in different cancers allowing them escape the immune system and hence, progress. We aimed to investigate the immunohistochemical expression of PD-L1 in GEP-NEN G3 and evaluate its correlation to clinical parameters. In a cohort of 136 patients, 14 (10%) expressed PD-L1 immunoreactivity; four (3%) patients in the tumor cells and 10 (7%) had immunoreactive immune cells. PD-L1 expression did not correlate to clinical parameters, progression-free survival or overall survival. We conclude that PD-L1 expression is present only in a subset of GEP-NEN G3 patients. Further studies are needed to fully understand the role of PD-L1 in patients with GEP-NEN G3, including the future possibility for treatment with immune checkpoint inhibitors.
|
|
| 9. |
- Almeamar, Hussein, et al.
(author)
-
Real-world efficacy of lutetium peptide receptor radionuclide therapy in patients with neuroendocrine tumours
- 2022
-
In: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 34:6
-
Journal article (peer-reviewed)abstract
- Lutetium peptide receptor radio nuclide therapy (Lu-PRRT) is an effective treatment for progressive, metastatic, somatostatin-receptor-positive, well-differentiated neuroendocrine tumours (WD-NETs). Here, we report a single centre experience of real-world efficacy, long-term side effects, and challenges of this treatment. This was a retrospective analysis. All patients linked with our centre who had Lu-PRRT were included. Clinicopathological data were analysed using descriptive statistics, Kaplan-Meier, and Cox regression. A total of 45 patients had Lu-PRRT, of those 30 (67%) were males, and 13 (29%) were more than 65 years old. The primary site was small intestine in 30 (67%) patients, pancreas in seven (16%) patients, and lung in three (7%) patients. The tumor was grade 1 in 15 (35%) patients, grade 2 in 22 (48%) patients, and grade 3 in six (13%) patients. A total of 41 (91%) patients had liver metastasis, and 20 (44%) patients had carcinoid syndrome. Lu-PRRT was the second-line therapy in all patients. Krenning's score was 4 in 36 (80%) patients and 3 in nine (20%) patients. The median waiting time to start Lu-PRRT therapy was 87 days. The median follow-up was 41 months. A total of 23 (51%) patients had a partial response, 18 (40%) patients had stable disease, and four (9%) patients had progression. None of the patients had a complete response. The median progression-free survival (PFS) was 38 months (95% CI: 25.8-50.1). The median overall survival (OS) was not reached. Nine patients died during follow-up (death from any cause). Prior treatment with targeted therapies or high dose somatostatin analogues were negative predictors of Lu-PRRT outcome (p-values of < .001 and < .045, respectively). There were two serious haematological toxicities, one patient developed acute myeloid leukaemia (AML), and the other developed chronic myeloid leukaemia (CML). Lu-PRRT is an effective second-line treatment for metastatic WD-NETs. The effect of targeted therapies on Lu-PRRT outcome was significant and needs to be clarified in further studies.
|
|
| 10. |
|
|
