Towards optimal personalized diet and vitamin supplementation in patients with a neuroendocrine tumor.

Patients with neuroendocrine tumors (NET) have a rare, slowly progressing
disease, which can produce bioactive amines. They may undergo many treatments
regimens such as surgery followed by systemic treatments with somatostatin
analogues. The tumor, the produced bioactive amines and these treatment
regimens can result in increased diarrhea and loss of critical food components
in the stools such as fat and fat-soluble vitamins. Which can lead to vitamin
deficiencies leading to several symptoms and complaints. In addition patients
can suffer from tumor related serotonin production leading to profuse diarrhea
and shortage of tryptophan. Tryptophan is a precursor of niacin (vitamin B3)
which is critical for normal cellular metabolism. Deficiencies of tryptophan
niacin can lead to symptoms including pellagra.
Strikingly little is known about how to supply for these vitamin deficits and
how NET patients can prevent deficiencies by diet interventions.
Patients with NET are faced with a serious chronic disease. This makes this
patient group extremely motivated to be involved in their treatment and to
*self-manage* their disease as much as possible.

This study aims to investigate if the proportion of NET patients with normal
vitamin values can be increased, with vitamin suppletion and a personalized
diet, measured with quantitative analysis of blood and urine. Secondary aims
are an improvement in nutrition state Patient-Generated Subjective Global
Assessment (PG/SGA), a decrease in distress on the distress thermometer,
improvement in quality of life as determined by the NET-specific EORTC
QLQ-GINET21 and the cancer-specific EORTC QLQ-C30. In additionFurthermore the
the self-reported healthy eating pattern will be evaluated and the
satisfaction of patients about the intervention will be assessed by a
semi-qualitative interview.

This is a single center 18-week open-label, non-comparative, single-arm,
intervention study. After inclusion and the first measurements, adult patients
with metastasized or iresectable NET will continue with four weeks of standard
treatment. After these four weeks participants with vitamin values below normal
will get vitamin suppletion for each deficient vitamin and all participants
will get the dietary intervention during 14 weeks. Effects of the intervention
will be evaluated by quantitative analysis of blood and urine and
questionnaires. The measurements, including; baseline characteristics,
quantitative analysis of blood and urine and questionnaires will be performed
at baseline (t=0), after 4 weeks (t=4) and after 18 weeks at end of study
(t=18). Furthermore at t=18 a semi-qualitative interview will be performed.

In the first four weeks after inclusion patients will get standard care. The
measurements, including; baseline characteristics, quantitative analysis of
blood and urine and questionnaires will be performed at baseline (t=0), after
four weeks (t=4), and after 18 weeks (t=18). Furthermore, at t=18 a semi
qualitative interview will be performed.
The first four weeks will be used to observe the variability of the vitamin
values during standard treatment. If patients have deficient vitamins at
baseline t=0 or Tt=4 weeks, we will start with vitamin suppletion. During the
intervention period, patients will in addition to standard treatment be
counseled by a dietician for 14 weeks. A personalized diet advice for each NET
patient will be based on the individual situation which includes the current
food intake of the patient, gastrointestinal complaints, the location of the
tumor, additional treatments like previous surgery and measured vitamin and
tryptophan levels.
All diets are based on the Dutch guidelines of the *voedingscentrum*. The
personalized diet advice provides patients insight in how they could adjust
their diet to experience fewer symptoms. Advices could consist of eating more
proteins, eating more soluble fibers or, for patients with pancreas
insufficiency, to motivate patients to eat fatty products in combination with
pancreas enzyme capsules. A diet with frequent small meals and with complex
carbohydrates, will be prescribed for patients with an insulinoma. Dietician
consults will be conducted by 1 out-patient visit and 3 follow up contacts in
week 5, 10 and 15 by telephone.

Most patients with a NET can live for many years with their disease. Disease
and treatment related vitamin deficiency, impaired nutrition state, distress
and an impaired quality of life can be an additional burden for these
patients. With this study we aim to detect that adequate vitamin suppletion and
additional a personalized diet will result in an increase in the proportion of
patients with normal vitamin values and an improvement in their nutrition
state, distress, quality of life and satisfaction in the intervention.