April 10, 2023 1

It Takes Gutsto be a Neuroendocrine Patient

perspectives on the importance of raising awareness about NETs as well as the challenges

a patient faces, and how the World NET Awareness Day campaign may benefit patients

April 10, 2023 2

WNAD

physiology

patient groups

patient journeys

issues

campaign

general info

disease

diagnosis

treatment

not all alike

strengths

weaknesses

challenges

years of misdiagnosis

assemble a team

medical tourism

smarter than physicians

basic

discussion points

survey of medical tourism

survey of misdiagnosis

focus on IBS

target GI specialists

aim for concrete objectives

WNAD

April 10, 2023 3

neuroendocrine tumors (NETs)

the physiology

April 10, 2023 4

Neuroendocrine System• We all have a neuroendocrine system, and it

can malfunction – leading to IBS, Crohn’s and neurendocrine cancer.

• A key component of neuroendocrine system (aside from pituitary) is the enteric nervous system, which consists of sheaths of neurons embedded in the walls of the intestine.– This ‘second brain’ contains some 100 million

neurons, more than in either the spinal cord or the peripheral nervous system.

April 10, 2023 5

Neuroendocrine Hormones• Neuroendocrine cells produce growth factor and

neurotransmitters– amines (eg- histamine, serotonin)– peptides (glucagon, calcitonin, pancreatic polypeptide)

• One of the most powerful neurotransmitters is serotonin.– Measured in picograms per milliliter. Only a teardrop in

the human body can cause dramatic effects.– serotonin is implicated in many syndromes such as autism,

migraines, anxiety, alcoholism and depression. – serotonin receptors are the target of a variety of

pharmaceutical and illicit drugs.

April 10, 2023 6

Seratonin in the Gut• Only 2% of serotonin is found in the brain.

– In the periphery, serotonin acts both as a gastrointestinal regulating agent and a modulator of blood vessel tone.

• Neuroendocrine disorders can manifest as tumors (NETs), typically in the GI tract.– Neuroendocrine tumors express serotonin 5-HT

receptors and can thus be targeted with somatostatin analogues (eg- Octreotide) and peptide receptor radiotherapy (PRRT).

April 10, 2023 7

NET Diagnosis• Diagnosis is difficult because the disease is

rare and symptoms are easily misunderstood.• The front line or first responders are gastro

intestinal (GI) specialist physicians.– Up to 80% of cases treated by GI physicians are

IBS and Crohn’s, which are non-specific in nature.– Functional GEP NETs (including PNETs) and

Pulmonary NETs typically present as IBS and neuroendocrine flushing.

– Misdiagnosis is very common.

April 10, 2023 8

NET Treatment• Like most rare diseases, treatment of NETs

involves a multidisciplinary medical team.• Preferred algorithm is: (a) locate and remove

primary, (b) treat distant mets with PRRT, (c) maintenance with somatostatin analogues.

• If properly managed, neuroendocrine disease is a chronic condition, not a terminal illness.

April 10, 2023 9

NET Patient Advocacy

the community

April 10, 2023 10

Different ‘Stripes’• The NET Patient Advocacy Groups (PAGs) have

different characteristics:– some are patient support groups– some are foundations funding research– some are quasi-professional bodies

• Tend to be driven by a single individual or a small group.

April 10, 2023 11

NET PAG Strengths• Offer conference programmes which provide

insights on treatment best-practice and networking to specialist physicians.

• Provide aggregation, making it easier for specialist physicians and pharma companies to engage with the patient community.

• Articulate concensus opinions, and speak in a collective voice (eg- in advocating government support for orphan drugs).

April 10, 2023 12

NET PAG Weaknesses• NET PAGs don’t own or control their online

communities.– ACOR is not specific to NETs - ACOR Carcinoid is

moderated by individual patient advocates.– Largest NETs Yahoo Group is run by an individual

patient advocate.

• NET PAGs have been fairly low tech, not early adopters of social media.

April 10, 2023 13

NET PAG Challenges• Partnerships with pharma companies (and

insurance companies) are suspect.

• Staying ‘out of the fray’. PAGs must ensure that communications in regard to health issues are apolitical.

• Tend to have issues with succession planning.

“Nothing having anything remotely to do with big Pharma will take place on my lists.” – Chas Schuetzen, Yahoo Carcinoid List Owner

April 10, 2023 14

the patients

patient journey

April 10, 2023 15

Years of Misdiagnosis“I had about every conceivable ultrasound, scope and lab test for a period of almost 5 years after I started to have intermittent, extemely painful abdominal spasms.The pains mimicked gall bladder pain,except that my gall bladdder had already been removed. I even had an ERCP with no improvement. In retrospect, the episodes were probably bowel obstruction or kinking caused by the many carcinoids and affected lymph nodes found in my terminal ileum during exploratory surgery.” - Richard in Minnesota

“I was misdiagnosed with menopause for about seven years...I was flushing during that time. Towards the end of that time, I started to have vague abdominal pain. I thought it was my gallbladder, as did my gastroenterolgist. A sono showed what they thought was 30-40 hemangiomas in my liver..the mri showed them also to be hemangiomas, except for two which were questionalbe...the ct and 5hiaa showed that it was, indeed, carcinoid.” – Janet in Long Island

April 10, 2023 16

Years of Misdiagnosis“For almost five years, I was diagnosed with IBS, gall bladder problems and everything else. I went into the emergency room hurting in my upper stomach area and they were looking at the gall bladder, which at that time was ok, but on the x-ray in the upper part, they saw something in my lower lungs, they then took an x-ray of the lungs and saw what they thought was carcinoid in my lungs. I had a biopsy the next day and it was confirmed that it was carcinoid cancer in my lungs. That was in 2003.” – Gloria in San Marcos (Texas)

“I was misdiagnosed, gastric acid, in stomach, flushing said to be panic attacks. diahrea said to be from lack of gall bladder. Liver mets id as hemangeomas in 2000, 2005 after bowel resection id as carcinoid mets [5 years].” – Jackie in Northern Ontario

“I am mid gut carcinoid. For years it was assumed I was having diverticuites.” – Phil in Michigan

April 10, 2023 17

Which Tests?• There is widespread ignorance of which tests

are important and when to perform them.– Chromagranin A (CgA) is a good marker for tumor

burdon and should be followed as a series.– Ki-67 is a good marker for proliferation, but needs

to be done only once and can be retrospective.

• Access to tests is a problem. – Ga-68 PET/CT not yet available in USA (Mar ’10).– CgA was only introduced in Singapore in 2009.

April 10, 2023 18

Need to Assemble a Team• Best practice is for the patient and caregiver

to assemble their own multidisciplinary team.– Led by medical oncologist as principal physician,

the team should include surgeon, endocrinologist, pathologist, radiologist, and radiation oncologist.

• Or, submit case for review at a regional center with a neuroendocrine tumor board. – Need to prepare electronic medical records.– Some hospitals dispute patient’s right to medical

records (education is required).

April 10, 2023 19

Journeys - Medical Tourism

“I travelled to Mayo Clinic, embolizations done in Manila, chemo in Singapore all in 2005. Tumors stable for the past 4+ years - under Sandostatin maintenance.” - Clarence in Singapore

“I went to Rotterdam for LU 177 and all my tumors disappeared. I visited 3 doctors Dr Kelsen in NY, Vinik Norfok VA and Dr Donhower in Baltimore. For surgery Dr Cameron and Choti in Baltimore, MD. Got Gallium PET in Chile and I discovered my bone cancer. Now my cancer is in remission.” – Gaston in Maryland

“I travel to California every 4 months to see Dr Wolin. Have recently been asked to join a clinical trail there and am in process of trying to make a decision. There is a lot of "what if's". Would pretty much go anywhere I needed to go to get the care I need but am fortunate Dr Wolin is so close.” – Nancy in Arizona

April 10, 2023 20

How Far Will You Go?“Left Michigan for Mayo for surgery, went to Norfolk conference in Virginia, went to Iowa to get referral to Basil, made 3 trips to Basil for Lu 177, now going to Iowa every 6 months and local oncologist gives Sando every 3 weeks.” - Sally in Michigan

“I have consulted on a regular basis with Dr. Warner in New York and now I consult with Dr. O'Dorisio in Iowa at least four times a year (Iowa is an easier trip from Michigan, I still love Dr. Warner). My local oncologist and Dr. O'Dorisio are part of what I call my carcinoid team. I have also done treatments with Dr. Riad Salem at Northwestern in Chicago and traveled to Basel Switzerland for two Y-90 DOTATOC Treatments. I have done other treatments and surgery, I have left town for most of them.” – Nancy in Portage (Michigan)

April 10, 2023 21

‘Smarter’ than Physicians• Canadian study* found physician ignorance to

be a major stumbling block. – Patients felt they had to advocate for themselves

and were much more positive if their provider encouraged them to be involved in decisions.

– Other patients found their physicians resistant to hear about new treatments or studies.

* “NETs Patient and Caregiver Perspectives (2009)” by Deana Midmer et al

“My doctor is teaching his students based on this case. He said if I find new material I should deliver it to him. He wants his patients involved.”

April 10, 2023 22

concerns patients have

the issues

April 10, 2023 23

Basic issues• Communicating about NETs can be very

difficult. Terms are not agreed and there is no standard protocol for treatment.

• Educational responsibility usually falls on the family caregiver.

• Need Internet access.

“My wife will be on line all night. If you are not that type of person… I feel sorry for you.”

April 10, 2023 24

Community Discussion Points• Why is there no simple screening test?• Single specialist or multi-disciplinary panels?• Early intervention or wait-and-see?• Targeted therapy: management versus cure?• Why are expensive pharmaceuticals not

covered by insurance?• Cancer families or cancer clusters (ie- genetic

or environmental factors)?

April 10, 2023 25

NETs Patient Medical Tourism• In the past 2 years, have you travelled out-of-

town to seek NETs-related diagnosis or treatment?

NETs Patient Medical Tourism(final results, 197 responses)

20%

11%

51%

18% no

no - but considering orplanning such travel

yes - travelled outsidemy state or province

yes - travelled outsidemy country

April 10, 2023 26

NETs Patient Medical Tourism• Lessons learned:

– 70% of patients travel out-of-state or province for specialist care (probably without insurance)

– even if you disqualify the ‘no’ votes, NETs patients really do travel more than other cancer patients

– anecdotal information (40 comments) suggest NETs patients travel not seeking reduced costs but best available care

– widespread perception that Europe is leading over USA in providing best diagnosis & treatment

April 10, 2023 27

NETs Patient Misdiagnosis(interim results, 87 responses)

29%

4%

13%

54%

No.

Yes, but it took lessthan 6 months.

Yes, and it took from6 months to 2 years.

Yes, and it took morethan 2 years.

NETs Patient Misdiagnosis• From first symptoms until NETs diagnosis,

were you misdiagnosed as having IBS, Crohn’s or another gastric disorder?

April 10, 2023 28

NETs Patient Misdiagnosis• Lessons learned:

– 67% of respondents were misdiagnosed with IBS– most functional NETs patients ‘originate’ from the

10% of general population who have gastric disorders such as IBS

– anecdotal information (29 comments) suggest functional lung carcinoid patients are also misdiagnosed as IBS

– if we want to screen for NETs, we can start with the IBS community, perhaps selecting those who are refactory to treatment, suffer longest, or who have had negative endo/colonoscopic exams

April 10, 2023 29

World NET Awareness Day

the campaign

April 10, 2023 30

Campaign Theme & Objective• Suggested theme: “Don’t blush about gastric

problems.”• To inform patients and physicians of the

importance of screening for NETs and the fact that if diagnosed and treated, NETs is usually a chronic disease and not a terminal illness.

• To change physicians’ mindset about IBS.– IBS is a temporary diagnosis, subject to periodic

review and further screening.

April 10, 2023 31

Target Audience• Primary audience should be people who have

been diagnosed with IBS, Crohn's Disease or who have vague abdominal symptoms but no definitive diagnosis (patients).

• Secondary audience should be gastro intestinal specialists (physicians).

April 10, 2023 32

Action Plan• Engage IBS support groups and medical

associations early. • Distribute brochures at GI-specialist events. • Use social media to reach out to the IBS

patient community.• Organise CME credit talks for GI-specialists. • Promote urinary 5HIAA and CgA blood tests.• Build awareness and pre-register attendees

for the events on 10 November.

April 10, 2023 33

Measurable Results• Success of the campaign can be measured.

– attendance at awareness talks & CME events– number of referrals to GI specialists– number of referrals for screening tests– number of NETs patients ‘discovered’

• All of these measurable results will benefit the patient community, and change the mindset of physicians to regard IBS as a ‘tentative diagnosis – always open to review’.

April 10, 2023 34

williamc@cnets.orgWrite me for further information

about NET patient advocacy.