Pancreatic neuroendocrine tumours: RADIANT news for everolimus in progression-free survival

2010 ◽  
Vol 7 (9) ◽  
pp. 8-9
Author(s):  
Brande Victorian
Keyword(s):  
Neuroendocrine Tumours ◽  
Progression Free Survival ◽  
Free Survival ◽  
Pancreatic Neuroendocrine Tumours

Alkylating agent rechallenge in metastatic pancreatic neuroendocrine tumours

2021 ◽  
Author(s):  
Ophelie De Rycke ◽  
Thomas Walter ◽  
Marine Perrier ◽  
Olivia Hentic ◽  
Catherine Lombard-Bohas ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Free Survival ◽  
Mgmt Expression ◽  
Pancreatic Neuroendocrine Tumours

A rechallenge is common after initial efficacy of alkylating-based chemotherapy (ALK) in pancreatic neuroendocrine tumors (PanNET). High MGMT expression seems associated with lower response to ALK. We aimed to evaluate the efficacy and toxicity of ALK rechallenge in PanNET. Secondly, to assess the evolution of MGMT expression under ALK. All consecutive patients with advanced PanNETs who received initial ALK (achieving tumor control) followed by a pause > 3 months, then an ALK rechallenge (ALK2) upon progression were retrospectively studied (Cohort A). Primary endpoint was progression-free survival under ALK2 (PFS2). The MGMT expression was retrospectively assessed by immunohistochemistry (H-score) in consecutive PanNET surgically resected following ALK (Cohort B). We foud that cohort A included 62 patients (median Ki67 8%), for which ALK1 followed by pause achieved an objective response rate of 55%, and a PFS1 of 23.7 months (95% IC, 19.8-27.6). ALK2 achieved no objective response, and stability in 62% of patients. The median PFS2 was 9.2 months (IC 95% 7.1-11.3). At multivariable analysis, a hormonal syndrome (p=0.032) and a pause longer than 12 months (p=0.041) were associated with a longer PFS2. In the cohort B (17 patients), the median MGMT H-score increased from 45 (IQR 18-105) before ALK, to 100 (IQR 56-180) after ALK (p=0.003). We conclude that after initial efficacy of ALK treatment, a pause followed by ALK rechallenge might be appropriate to prolong tumor control, improve quality of life and limit long-term adverse events. Increased MGMT expression under ALK might explain low efficacy of ALK rechallenge.

Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumours

2019 ◽  
Vol 12 (2) ◽  
pp. 126-134 ◽  
Author(s):  
Shahad Alsadik ◽  
Siraj Yusuf ◽  
Adil AL-Nahhas
Keyword(s):  
Side Effects ◽  
Effective Treatment ◽  
Radionuclide Therapy ◽  
Neuroendocrine Tumours ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Treatment Modalities ◽  
Effective Treatment Option ◽  
Peptide Receptor ◽  
Pancreatic Neuroendocrine Tumours

Background: The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management. Objective: The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours. Methods: A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs). Results: PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients’ Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible. Conclusion: PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.

Bronchial neuroendocrine tumors: A retrospective review of management and outcomes in 116 patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17543-e17543
Author(s):  
Marinos Pericleous ◽  
Heather Lumgair ◽  
Johnathan Reiner ◽  
Laura Marelli ◽  
Martyn Caplin ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Survival Rates ◽  
Treatment Algorithm ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Large Cell ◽  
Diagnostic Features ◽  
Free Survival ◽  
Histopathological Classification

e17543 Background: Bronchial neuroendocrine tumours, represent 1–3% of all primary lung tumours and 25% of all neuroendocrine tumours (NETs). They are classified into: typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell lung carcinomas (SCLC). The aim of our study was to assess diagnostic features, management and outcome, focusing on the differences between TC and AC. Methods: 116 patients were identified from our NET database. WHO histopathological classification was used. Follow-up was complete in all patients (mean follow-up 59.8 months). Disease-free survival (DFS), and progression-free survival (PFS) were evaluated for each therapy. Results: The average age of presentation was 55.30 years (range 16-85 years, M:F ratio=1:1.5). The commonest presenting symptom was cough (19%) followed by haemoptysis (18%). 36% were TC, 45% AC, and 19% LCNEC/SCLC. 16% TC and 28% AC patients had metastases at diagnosis. Octreoscan was positive in 76% TC and 66% AC. In 2 patients with TC and negative Octreoscan, Ga-68 Octreotate PET showed avid uptake in lung lesions. 46 patients had surgery. In 35 of AC, the disease relapsed (DFS=29.8 months) compared to 24% TC (DFS=48months). 12 patients received somatostatin analogues (SSTA) with PFS for TC 60 months and AC 21 months. 16 patients received systemic chemotherapy with PFS for TC 72 months and AC 21 months. 4/5 patients achieved disease stability with 90Yttrium-DOTAoctreotate. 5-years survival after surgery, chemotherapy or SSTA, was 91%, 86% and 81% respectively. Overall five year survival was 91% (100 % TC, 75% AC). Conclusions: AC and SCLC/LCLC more often present with metastatic disease with shorter DFS and PFS compared to TC. Molecular imaging is helpful for staging and predicting appropriateness for SSTA or radionuclide targeted therapy. Surgery confers the best survival rates. AC have higher relapse rates and metastatic potential. Further clinical trials are required to define the best treatment algorithm.

scholarly journals Sequence of therapy and survival in patients with advanced pancreatic neuroendocrine tumours

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
E. S. Tsang ◽  
J.M. Loree ◽  
C. Speers ◽  
H.F. Kennecke
Keyword(s):  
Neuroendocrine Tumours ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Treatment Modalities ◽  
Primary Role ◽  
First Line ◽  
Optimal Sequence ◽  
Systemic Treatments ◽  
Pancreatic Neuroendocrine Tumours ◽  
Line Of Therapy

Background Pancreatic neuroendocrine tumours (pnets) often present as advanced disease. The optimal sequence of therapy is unknown. Methods Sequential patients with advanced pnets referred to BC Cancer between 2000 and 2013 who received 1 or more treatment modalities were reviewed, and treatment patterns, progression-free survival (pfs), and overall survival (os) were characterized. Systemic treatments included chemotherapy, small-molecule therapy, and peptide receptor radiotherapy. Results In 66 cases of advanced pnets, median patient age was 61.2 years (25%–75% interquartile range: 50.8–66.2 years), and men constituted 47% of the group. First-line therapies were surgery (36%), chemotherapy (33%), and somatostatin analogues (32%). Compared with first-line systemic therapy, surgery in the first line was associated with increased pfs and os (20.6 months vs. 6.3 months and 100.3 months vs. 30.5 months respectively, p < 0.05). In 42 patients (64%) who received more than 1 line of therapy, no difference in os or pfs between second-line therapies was observed. Conclusions Our results confirm the primary role of surgery for advanced pnets. New systemic treatments will further increase options.

scholarly journals CUX1—Transcriptional Master Regulator of Tumor Progression in Pancreatic Neuroendocrine Tumors

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1957
Author(s):  
Sebastian Krug ◽  
Julia Weissbach ◽  
Annika Blank ◽  
Aurel Perren ◽  
Johannes Haybaeck ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Model ◽  
Neuroendocrine Tumours ◽  
Tumour Progression ◽  
Free Survival ◽  
Treatment Naïve ◽  
Pancreatic Neuroendocrine Tumours ◽  
The Impact

Recently, we identified the homeodomain transcription factor Cut homeobox 1 (CUX1) as mediator of tumour de-differentiation and metastatic behaviour in human insulinoma patients. In insulinomas, CUX1 enhanced tumour progression by stimulating proliferation and angiogenesis in vitro and in vivo. In patients with non-functional pancreatic neuroendocrine tumours (PanNET), however, the impact of CUX1 remains to be elucidated. Here, we analysed CUX1 expression in two large independent cohorts (n = 43 and n = 141 tissues) of non-functional treatment-naïve and pre-treated PanNET patients, as well as in the RIP1Tag2 mouse model of pancreatic neuroendocrine tumours. To further assess the functional role of CUX1, expression profiling of DNA damage-, proliferation- and apoptosis-associated genes was performed in CUX1-overexpressing Bon-1 cells. Validation of differentially regulated genes was performed in Bon-1 and QGP1 cells with knock-down and overexpression strategies. CUX1 expression assessed by a predefined immunoreactivity score (IRS) was significantly associated with shorter progression-free survival (PFS) of pre-treated PanNET patients (23 vs. 8 months; p = 0.005). In treatment-naïve patients, CUX1 was negatively correlated with grading and recurrence-free survival (mRFS of 39 versus 8 months; p = 0.022). In both groups, high CUX1 levels indicated a metastatic phenotype. Functionally, CUX1 upregulated expression of caspases and death associated protein kinase 1 (DAPK1), known as mediators of tumour progression and resistance to cytotoxic drugs. This was also confirmed in both cell lines and human tissues. In the RIP1Tag2 mouse model, CUX1 expression was associated with advanced tumour stage and resistance to apoptosis. In summary, we identified the transcription factor CUX1 as mediator of tumour progression in non-functional PanNET in vitro and in vivo, indicating that the CUX1-dependent signalling network is a promising target for future therapeutic intervention.

Long-term survival and toxicity in patients with progressive advanced neuroendocrine tumors treated with lutetium peptide radiolabelled radiotherapy: A Western Australian long-term follow-up study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16202-e16202
Author(s):  
Kim Robyn Kennedy ◽  
Phillip Claringbold ◽  
William Macdonald ◽  
Glenn Boardman ◽  
David Turner Ransom ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumours ◽  
Progression Free Survival ◽  
Somatostatin Analogue ◽  
Term Survival ◽  
Free Survival ◽  
Follow Up Study ◽  
Long Term Follow Up

e16202 Background: There are limited treatment options for advanced neuroendocrine tumours, and radiolabelled somatostatin analogues have shown favourable safety and efficacy over other existing treatments. Lutetium Octreotate has been shown to be the somatostatin analogue of choice in Peptide Radiolabelled Radiotherapy (PRRT) for advanced neuroendocrine tumours (NETs). Methods: We conducted a retrospective review of the long term safety and survival outcomes of 104 patients prospectively treated on the CLEMENT1, CLEMENT2, NETTLE, and NETT VALuE trials where patients with advanced progressive NETs were treated with Lutetium Octreotate PRRT in Perth, Western Australia. With a median follow-up time of 68 months, this is the longest follow-up study of advanced NETs treated with Lutetium PRRT in the literature to date. Results: Results showed comparable periods of disease stability as other studies, with median progression free survival of 43 months, and superior survival to other series, with a median survival of 71 months. There were patients who had very durable responses, with five year overall survival 61.5%, five year progression free survival 30.1%, 10 year overall survival 30.1%, and 10 year progression free survival of 29.3%, demonstrating Lu 177 can provide a very long duration of response in some patients. PRRT treatment was well tolerated with 1.9% of patients suffering long term renal impairment, and 1% with long term mild thrombocytopenia attributed to PRRT. Importantly, there was a higher rate of MDS and leukaemia in our series (6.7%), which is likely attributed to the longer period of follow-up with all except one case occurring 48 months after PRRT treatment, which is later than the median follow up in most other studies. Conclusions: Overall, this study showed that Lutetium PRRT remains an efficacious and well tolerated treatment in long term follow-up. For clinicians deciding on the timing of PRRT for individual patients the 6.7% long term risk of MDS/leukaemia needs to be balanced against the 29.3% PFS at 10 years. Clinical trial information: ACTRN12610000440022.

scholarly journals Predictive factors of response to mTOR inhibitors in neuroendocrine tumours

2015 ◽  
Vol 23 (3) ◽  
pp. R173-R183 ◽  
Author(s):  
Maria Chiara Zatelli ◽  
Giuseppe Fanciulli ◽  
Pasqualino Malandrino ◽  
Valeria Ramundo ◽  
Antongiulio Faggiano ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Neuroendocrine Tumours ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Free Survival ◽  
Development Of Resistance ◽  
Imaging Markers ◽  
Intensive Investigation ◽  
Recent Demonstration

Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs.

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