Purpose:
This study will evaluate members in families with a history of small bowel carcinoid cancer
to study the natural history of those family members that have the disease, determine ways to
improve early detection by performing surveillance on those at risk but without disease and
to identify the gene(s) that may cause the tumors. Familial carcinoid tumors usually
originate in hormone-producing cells that line the small intestine or other cells of the
digestive tract. The tumors are slow-growing and usually take many years before they cause
symptoms. It is known that these tumors occur more often in some families and are then passed
from one generation to the next by inherited genes.
Members of families, including all siblings and offspring in which two or more immediate
blood relatives have had small bowel carcinoid tumors are eligible for this study. In some
cases unaffected spouses of family members diagnosed with carcinoid cancer are also requested
to participate by donating a sample of blood only.
Participants undergo a medical evaluation every 3 years during a 3- to 5-day hospital stay at
the NIH Clinical Center. All participants have a personal and family medical history obtained
and undergo a physical examination, blood and urine tests.
People who already have a small bowel carcinoid tumor or are at risk of developing a
carcinoid tumor have some or all of the following procedures to determine the presence of
carcinoid tumor and its (omit next two words- location or) spread to other areas of the body:
- Video Capsule Endoscopy: Visualization of the gastrointestinal tract by ingesting a
disposable, "vitamin-pill sized" video capsule that has its own camera and light source.
- CT of the chest abdomen and pelvis with oral and IV contrast : X-ray examination of the
chest, abdominal and pelvis organs.
- 18 FDOPA Positron emission tomography (PET) with CT for localization: Nuclear imaging
scan to look at tumor activity.
- MRI Liver with contrast - to determine if disease has spread to liver
- Gallium 68 PET/CT-limited to individuals that have residual tumor.
- Clinical and research blood work
Should mid gut carcinoid tumors be found every participant will be assisted in determine what
the best course of treatment will be for them.
Study summary:
Study Description:
This study is designed as a prospective evaluation for diagnostic screening, genotyping and
natural history of participants belonging to kindreds with familial carcinoid tumor.
Objectives: Primary Objective:
Study the natural history of familial carcinoid tumors: incidence, age of onset, symptoms,
the appropriate diagnostic (biochemical and imaging) modalities, location, histology and
metastatic potential of the tumors, metabolic sequelae of the tumor, and clinical and
biochemical prognostic factors.
Secondary Objectives:
- Screen for occult disease and determine whether early detection affects the natural
history of the disease.
- Compare the sensitivity and specificity of various imaging tomography (CT) with IV
contrast and oral Volumen, 18FDOPA PET/CT scan, [68Ga] DOTATATE PET/CT scan and
endoscopic modalities for diagnosing and following carcinoid tumors.
- Collect tumor specimens for histologic evaluation, culturing of intestinal organoids,
and genotyping (including DNA and RNA sequencing).
- Sequester DNA from peripheral blood for genotyping (including sequencing) with the
intention of localizing a susceptibility gene/s responsible for the familial occurrence
of the disease.
Criteria:
- INCLUSION CRITERIA:
There are four types of participants who will be included in this protocol as outlined
below.
In order to be eligible to participate in this study, an individual must meet all of the
following criteria for their group:
Group 1 (Arm 1 or Arm 2)
- Male and female subjects >= 18 years of age
- Have a diagnosis of small intestinal carcinoid tumor
- Have at least one blood relation with a diagnosis of either small intestinal,
pulmonary, kidney or gastropancreatic neuroendocrine tumor or metastatic
neuroendocrine tumor of unknown primary
Group 2 (Arm 1 or Arm 2)
- Male and female subjects >= 18 years of age
- Has multiple synchronous primary small intestinal tumors
Group 3 (Arm 1 or Arm 2)
- Male and female subjects >=18 years of age
- Does not have a diagnosis of carcinoid tumor
- Has one of the following:
- at least two blood relatives with any combination of diagnoses of small
intestinal carcinoid tumor, a pulmonary, kidney, gastropancreatic neuroendocrine
tumor or metastatic neuroendocrine tumor of unknown primary OR
- has at least one blood relative with multiple, synchronous primary small bowel
tumors
Group 4 (Arm 2 only)
- Male and female subjects >= 18 years of age
- Not biologically related to the participating family but has offspring who is/are
blood relative(s) of a participating subject.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation
in this
study:
1. Members of families with multiple endocrine neoplasia (MEN) I, MEN II or other
familial tumor syndromes such as Von Hippel Lindau Syndrome and Neurofibromatosis type
I and type II for which there is a known genetic predisposition to non-carcinoid
tumors as well as
carcinoid tumors will be excluded from the study.
2. Any condition which, in the opinion of the investigator, would make it unsafe to
participate or would prohibit completion of the protocol.
3. Inability to provide informed consent
4. Pregnant or breastfeeding