Towards optimal personalized diet and vitamin supplementation in patients with a neuroendocrine tumor; a pilot study

Patients with neuroendocrine tumors (NET) have a rare, slowly progressing
disease. Therefore they undergo many treatments such as surgery followed by
long-lasting systemic treatments with somatostatin analogues. These procedures
can each result in increased diarrhea and loss of critical food components in
the stools such as fat. This can lead amongst others, to major loss of
fat-soluble vitamins. Those patients who in addition have an ongoing serotonin
production may experience shortage in the circulating essential amino acid
tryptophan. Serotonin is derived from the essential amino acid tryptophan.
Tryptophan is a precursor of niacin (vitamin B3) which is critical for normal
cellular metabolism. In case of high serotonin production in neuroendocrine
tumor patients tryptophan and/or niacin can be deficient leading to symptoms
including pellagra. Suppletion of tryptophan might facilitate serotonin
production and therefore, is undesirable in patients with serotonin producing
neuroendocrine tumors.
Strikingly little is known about how NET patients should be best supported for
the deficits they develop during their long-lasting disease. Also the precise
effect of diet advices for diarrhea and fat-soluble vitamins and vitamin B3, in
this patient group is unknown.
Patients with NET are faced with a serious chronic disease. This makes this
patients 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 optimal personalized consultation by a
dietician for a healthy diet focused on food which contains sufficient vitamins
and minerals improves gastrointestinal symptoms as determined by an improved
score in the gastrointestinal symptoms of the NET specific EORTC QLQ-GINET21 at
end of study. Secondary aims are decrease in distress on the distress
thermometer, improvement in quality of life as determined by the
cancer-specific EORTC QLQ-C30, and the other constructs of the EORTC
QLQ-GINET21, empowerment (subscales of the Construct Empowering Outcomes
questionnaire) at end of study, an improvement in nutrition state
(Patient-Generated Subjective Global Assessment PG/SGA) and normalization of
vitamins and tryptophan levels at end of study measured with quantitative
analysis of blood and urine.

This is a single center 18-week open-label, non-comparative, single-arm,
experimental pilot study. In this pilot study we want to examine the effect
sizes of the gastrointestinal symptoms of the NET specific EORTC QLQ-GINET21 of
the patients after the dietary intervention.
. Four weeks after inclusion adult patients with metastasized NET and chronic
use (>6 months) of a somatostatin analogue will start with the dietary
intervention. Effects of the intervention will be evaluated by questionnaires
and vitamin values in blood and urine.
Patients fill out these questionnaires at baseline, after four weeks, and after
18 weeks. Furthermore at baseline, after four weeks and then after 18 weeks
vitamin values in blood and urine will be measured and at baseline.

In the first four weeks after inclusion patients will get standard care.
Patients fill out the questionnaires at baseline, after four weeks, and after
18 weeks. The first month will be used to observe the variability of the scores
of the gastrointestinal symptoms of the QLQ-GINET21. Four weeks after inclusion
patients will be counseled by a dietician for 14 weeks. A tailored diet advice
for each NET patient will be based on the individual situation which includes
gastrointestinal complaints, the location of the tumor, additional treatments
like previous surgery and measured vitamine and tryptophan levels.
All diets are based on the Dutch guidelines of the *voedingscentrum*. The
tailored 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. If medically indicated patients
will be supplied with supplements.
Dietician consults will be conducted by 1 out-patient visit and 3 follow up
contacts (by visit/telephone or video consultation system).

Most patients with a NET can live for many years with their disease. Disease
and treatment related diarrhea and vitamin deficiency can be an additional
burden for these patients. With this study we aim to detect that additional
dietician consults and adequate vitamin suppletion will result in a difference
in gastro-intestinal symptoms and distress and, in addition to adequate vitamin
and tryptophan levels.