Highlights from ENETS 2019

The meeting was well attended with 1600 registered for the main meeting and 830 for the postgraduate course.

Themes that came up were:

Lutetium therapy is becoming a norm for small bowel net 2nd line and there was some evidence presented that it may be used 2nd line in pNET also. Day case therapy is possible although there is great variability between countries, and there are a lot of funding issues.

A session on bronchial NET was of interest and avoiding parenchymal resection using sleeve resections was emphasised. It seems there is still some resistance to using Ki67 in prognosticating bronchial nets, although there is now good evidence of its validity.  

Juan Valle gave a talk on G3 NEC and response to chemotherapy. A scoring system was shown for deciding on response to platinum based chemotherapy. 

A  meta analysis of chemotherapy for WD small bowel NET was presented showing ORR of only 11% and was declared a lost cause. For pNET ,Trial E221 comparing temozolamide vs tem/cap  showed overall response rate as 27 vs 30 % but baseline grades were not equal so hard to compare the 2 groups.

A case was made for repeat biopsy of pNET metastases before proceeding to 2nd of 3rd line therapy in view of changes in grade with time.

Several references were made to the publication of improved QoL after PRRT. There is now good evidence of prolonged time to deterioration in QoL with this therapy, although the patients were not blinded in the NETTER-1 study, hence QoL may have some bias. Telotristat has shown some improvement in QoL scores compared to placebo in a double blind trial. The There have been some changes in QoL using FACT-G after everolimus in the radiant trials and the oblique trial show no deterioration in QoL over 6 months of everolimus therapy.

Evidence of altered outcomes in pNET with genomics was discussed. Mutations in ATTRX, DAX , MEN1 and in mTOR activation may have prognostic significance but are not in routine clinical use at present in most centres. PDL-1 expression did not appear to show any change.

Theragnostics and radiomics are new terms related to adjusting therapies based on imaging techniques. Modified RECIST and Choi criteria were discussed as well as differentiation of G2 to G3 using radiomics.  NET test  prediction of survival was discussednad it was felt futher validation was needed. Several posters supported its use in clinical practice. 

A nomogram for prediction of response/ survival was presented by Jaume Capdevilla

The 10th anniversary of the centres of excellence programme was celebrated with 50 current centres, of which 10 are in UK. Average new patient numbers were 135 per year with only a median of 8 patients per centre recruited to trials. 

Rob Coleman presented data on bone mets in cancer with some extrapolation of data for NET.  Inhibition of osteoclast activity is key to therapy. Denosumab may be slightly better than Zoledronate but has more side effects, and is much more expensive and causes rebound when stopped. Zoledronate given every 3 months is as good as monthly , hence he suggested this bisphosphonate given every 3 months iv in NET patients. Radium 223 was suggested as an alternative for bone mets.

Talks on immune landscape and immune-editing were of interest. Check point molecule may make cancer cells invisible or untouchable . This was the rationale for checkpoint inhibitors but so far there is little evidence of efficacy in NET.  CAR-T therapy was discussed which has become a therapy for haematological malignancy  and could be used in solid tumours, but with more difficulty. In theory could be a therapy for NET but no evidence as yet.

A talk on nuclear medicine scanning showcased Extendin scanning for insulinoma, CXCR4 scans and also combined PET with MRI. 

An Australian series showed long term PRRT treatment related myeloid neoplasia ( T-MN) in 4.8 % of case. All pts were pretreated with chemotherapy. Malignancy occurred at a median of 25 months post PRRT.

Simron Singh gave a talk on health economics pointing out that there is very poor data for NET therapies at present. In many countries there was a toxic choice where finance was being restricted. Many therapies in NET look expensive and not good value compared to other diseases which is going to be a challenge. 

Endpoints for trials were discussed with apparently different conclusions from 2 concurrent sessions! The debate is about PFS as an endpoint. Combined endpoints and common outcome sets were discussed for trials. A patient reported experience measure was presented which aims to let patients report their experience of care within their centres of excellence. An  Australian patient support group is devising a registry for patients with a self reporting app which was well received. 

A NEXTgen meeting was held with about 50 young persons attending who plan to form their own group within ENETS for sharing research ideas, data and clinical information. Any young researchers wanting to join this group that were not at the meeting should contact Leah at [email protected]

Selected abstracts were once again presented in style by Bob Jensen.

Some highlights are listed:

Cancer associated fibroblasts are able to induce resistance to everolimus. 

Non-coding RNA is present in NET cells and occurs in greater frequency than coding RNA

Micro RNAs are often present in NET patients and may relate to metastasis development.

More abstracts on outcomes of  Pancreatic nET <2cm appeared, and watching these appeared to be relatively safe if they were surveyed regularly.

Various nomograms have bee developed for outcomes in  NET including the NEP score. 

Surgical series shoed in 10 out of 10 resected liver metastases there were micrometastases in surrounding resected liver. 

Various abstracts on biomarkers such as the NET test and vasostatin as predictive of progression. 

Increase in Ki67 over time in sequential biopsies was a good predictor of progression. 

Tumour growth rate (tgr)  a good predictor of survival,

Biliary stone disease common when using SSRA’s

Lenvatinib in Pan NET showed ORR of29% which is as high as some licenced therapies.

IN a retrospective series PRRT in pancreatic NET appears to have a better and more prolonged response than chemotherapy or everolimus.

Nuclear medicine abstracts showed FDG parameters may be better than Ki67 at predicting prognosis. Using FDG with Dotatate PET may preclude need for sequential biopsies. 

5FU therapy may upregulate the sensitivity of NET to PRRT.

Liver metastases resection once again showed evidence for and against. 

Lymph nodes dissection may not change survival in pancreatic NET

There are oestrogen/Progesterone receptors on many NET cells. Might lead to therapeutic possibilities.

Clinical trials. Jaume Capdevlilla


Spartalizumab in bronchial NET

Seqtor- due to report 2020

Telefirst- in set up. 

SENECA. Folfiri vs captem for grade 3 NET

NET 02 irinotecan vs docetaxel – in set up

DUNE- 2 immunotherapies in lung, gi, pNET and grade 3

Cabatem trial: Cabozatinib and Alezulimab in wdnet


Words by Prof John Ramage