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Notes from ENETS 2017

Inca blog Bill ENETS 1
Notes from ENETS 2017

 

Blog post by Bill Claxton.
Barcelona 8-10 March

Notes from ENETS 2017

ENETS is the world’s premier conference on neuroendocrine cancer, this year attended by more than 1200 physicians and a few dozen patient advocates. The ENETS conference highlighted the latest in understanding in tumor biology as well as offering the most current and relevant aspects of neuroendocrine tumor (NET) advances in diagnostics and therapeutics.

 

Bill Claxton, one of the founders of CNETS Singapore, is a well known patient advocate. Bill has been involved in video recording of many international carcinoid and neuroendocrine tumor conferences. These videos provide an excellent resource for patients, caregivers and physicians. Read more from Bill, Good news for NET Cancer
Learn more; Webinar Series with NET Cancer specialists and Webinar for Lung NETs

 

 

Newsworthy

– The passing of Dr Dik Kwekkeboom was acknowledged with a moment of silence. Dr Kwekkeboom passed away on 8 March from complications related to a recent stroke. He was one of my nuclear medicine physicians and an extraordinary leader in the field. Since 1998, more or less since the invention of octreoscan, he practiced nuclear medicine at Erasmus Medical Center in Rotterdam, working in partnership with Dr Eric Krenning. He was focused on Lu-177 PRRT and authored a number of articles and textbooks, mainly in endocrinology and peptide receptor scintigraphy. His papers concluded that PRRT works better in patients who are naive to somatostatin analogs, and those with small distant metastases, arguing for use of PRRT as a 2nd line therapy (ie- after surgical excision of the primary). This was revolutionary, since many guidelines advise using targeted radiation only upon disease progression. Dr Kwekkeboom will be missed by medical colleagues and patients like me.

– Dr Kjell Oberg of Upsalla University Hospital in Sweden received the ENETS 2017 Lifetime Achievement award. At the award ceremony, he gave a lecture sharing the history of his work in discovering tachykinins in carcinoid, developing CgA and Ki67 tests, developing the first oncolytic virus treatment for NET patients and many other achievements.

 

Symptoms

– Neuroendocrine cell function is to secrete hormones and peptides on demand. However only 20% of pNETs tumors and 30% of mid-gut carcinoids (specifically those with liver mets) are ‘functional’ in the sense of secretions that produce gross symptoms.

– Cardiac heart disease used to occur in 50% of NET patients, now it’s down to 18%. But vigilance is still warranted.

– A study by nurses reported that small intestine microbial growth (SIBO) occurs in a large number of NET patients in clinic, esp after GI surgery, diagnosed with breath test esp hydrogen and methane. This is treated by antibiotics and probiotics.

 

Biomarkers

– Chromogranin A (CgA) is colocalized in GI neuroendocrine cells with serotonin. Similar to ergotamine, CgA is a vaso-constrictor, causing narrowing of the blood vessels. Both are known to cause valvular fibrosis (news to me as a user of Cafergot for migraines).

– There is a very good paper on unmet needs in biomarkers in Lancet (2015) by Dr Oberg et al, “Concensus on Biomarkers“.

– There is wide support to the use of emerging biomarkers in multianalyte technologies based on neuroendocrine tumour genomics, particularly the NETest by Wren Laboratories.

– Much of the focus on cancer biomarkers is now on circulating tumor cells (more info). 50% of NET patients have circulating tumor cells. CTCs can give an early warning of tumor progression – before scans. However the Oberg paper reports that: “No overall consensus was achieved about whether circulating tumour cells correlated with tumour burden, grade, or prognosis, and participants agreed that further studies on the use of circulating tumour cells as biomarkers are needed.” @\Notes From ENETS 2017.docx, rev: 19-Mar-17 Page 2 of 3

 

Genetics

– Predictive markers for resistance to Evirolimus were discussed, mostly focused on the mTor pathway and specific genetic alterations (this work is beyond my current understanding).

– The term ‘omics’ was often used in the conference. ‘Omics’ refers to treatment selection based on genomics, a technique which is improving patient outcomes (more info).

 

Pathology

– Pathological classification of a tumor as being of neuroendocrine origin requires >50% chromagranin or synatophysin on tissue stains. I thought it was >50% chromagranin and >50% synatophysin (more info).

– Pathological diagnosis is definitive – the cancer registrar is not allowed to overrule pathologist.

– Tumor vascularity (presence of blood vessels) is highly variable, more so in small indolent lesions (in pNETs). In well-differentiated NETs, having blood vessels near mitotic cells is normal (this was counter-intuitive to me, because I thought that only poorly differentiated NETs would be rich in blood vessels).

– Recent studies have shown that not all G3 tumors have a high proliferation rate. Some are relatively indolent (more info).

– In pNETs, genomic analysis has identified different pathologies associated with different molecular subtypes (more info).

– The World Health Organisation is planning a new classification scheme for tumor grade: G1, G2, and G3 NET (for slowly proliferating tumors) and G3 NEC (for rapidly proliferating tumors).

– To discriminate between G3 NET and NEC, there is no cut-off based on Ki67. You have to look closely at the pathology report.

– Aurel Paren says there is no evidence for progression from NET to NEC. That is, G2 NET progresses to G3 NET with (much) better prognosis than NEC. It does not become a NEC (thisis of interest to me because I have a case of diagnosed de-differentiation from G1 -> G2 [6 years out] -> G3 [12 years out]).

 

Imaging Studies

– High ADC is corelated with tumor aggressivity. Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue, and is commonly clinically calculated using MRI.

– FDG PET can be a better predictor of survival than Ki67 (more info). Using both modalities is best of course.

– Dr Guido Rindi (well-known NET pathologist) reports that, while biopsy is still the mainstay of diagnosis, there is growing evidence for the use of (non-invasive) molecular imaging as an alternative or adjunct to pathology (more info).

– Imaging is better than biopsy for heterogenous tumors, says Andreas Kjaar (more info).

– FDG PET can better discriminate phenotype and prognosis than tumor grading.

– One presentation, citing work by Dr Rusniewski et al, dealt with analytical measurements of RECIST values, so called ‘tumor kinetics’. The idea is that slope of the tumor growth curve is a predictor for outcome. The measurement of % change in tumor growth (slope) is calculated as tg = 3 x log(d2/d1) over some period of time (more info). @\Notes From ENETS 2017.docx, rev: 19-Mar-17 Page 3 of 3

– 18F-fluorothymidine imaging (FLT) is increasingly used in small cell lung cancers and there is some interest in comparing FLT vs FDG as a predictor for tumor progression in NETs. Some have reported that FLT provides an earlier indication of therapy response and is prognostic. But not everyone agrees (more info).

 

Treatments

– Several studies demonstrate the clinical benefit of multidisciplinary care (more info).

– Alpha interferon still has a role says Dr Oberg. It is useful in the 10-15% of NET patients who are receptor negative, and can also be helpful in SSA dose escalation cases.

– Both everolimus and a-interferon are suitable if a patient is SSA receptor negative. This occurs in 15% of GI, 30% of pancreas, and 50% of lung neuroendocrine tumors.

– Endoscopic Ultra Sound guided Radio Frequency Ablation (EUS RFA) can be used for non-operable pNETS, eg- as an alternative for Whipple (more info). But one must beware that ablation is hit-and-miss, not curative and potentially harmful.

– A novel tumor marker known as urokinase receptor (uPAR) can be used for imaging during surgery. A high expression of uPAR is a predictor cancer malignancy and metastases (not specific to NETs), but because it can be visualised inter-operatively, uPAR can be used for surgical imaging and robotic surgery (more info).

– A study by Dr Fazio has shown that drug holidays do not affect treatment efficacy. I already knew this was true for PRRT, but Dr Fazio was looking at drugs like Sunitanib.

 

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ENETS, the European Neuroendocrine Tumor Society

ENETS, the European Neuroendocrine Tumor Society was founded in 2004 and the society members, currently numbering nearly 1,400, bring a variety of expertise from such fields as oncology, pathology, radiology, nuclear medicine, endocrinology, surgery and gastroenterology to ENETS. Neuroendocrine tumors (NETs) present numerous complex clinical problems. Due to their relatively rare occurrence, research and patient care guidelines since the 1990s have been lacking. As a result ENETS was founded. Learn more at www.enets

 

The International Neuroendocrine Cancer Alliance’s (INCA) Blog

INCA photos from ENETS 2017 at Flickr https://www.flickr.com/photos/147932663@N08/sets/72157680235606481

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