Within the framework of a longitudinal follow-up study, we aim to determine the excess number of detected and surgically resected high-grade premalignant lesions and early stage pancreatic cancers resulting from yearly testing using EUS in a cohort…
ID
Source
Brief title
Condition
- Other condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Health condition
pancreatic cancer
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The resectability, stage distribution and survival of pancreatic cancer cases
in the screened high risk population as compared to the general population.
Secondary outcome
(I) The number of screen detected and resected high-grade dysplastic lesions
(II) The number of intensified follow-up periods
(III) The yield of EUS as a screen tool for pancreatic cancer and it*s
precursor lesions: e.g. detection rate of solid and cystic lesions
(VI) The number of cases that wrongfully underwent surgery, due to false
positive tests
(V) The natural course of development of lesions that are identified during
surveillance.
(IV) Identify potential biomarkers that can predict the development of
high-grade dysplasia or early pancreatic cancer
Background summary
With a mean survival after diagnosis of <6 months and a 5-year survival of <6%,
pancreatic cancer has one of the poorest prognosis of all human cancers. Since
this poor prognosis is mainly caused by the late occurrence of symptoms, one of
the most promising means to fight pancreatic cancer death is early detection at
a stage when the cancer is not yet symptomic or, preferably, at its benign
precursor stage. In particular when this early detection is tailored towards a
well-defined population of individuals that carry a significantly increased
risk of developing pancreatic cancer (relative life-time risk: 2.3-132!) the
potential health gains are enormous.
Preliminary data (including the results of our own ongoing pancreatic cancer
surveillance study) is starting to show that endoscopic ultrasonography (EUS)
and magnetic resonance imaging (MRI) are promising techniques to detect
non-invasive precursor lesions and asymptomatic early stage pancreatic cancer
in high-risk individuals. However, we currently lack data driven evidence
showing that the benefits of screening and identification of early stage
lesions outweigh the negative side effects of (over)treatment and costs. In
order to remedy this lack of knowledge, longer-term follow-up studies are
urgently needed.
Study objective
Within the framework of a longitudinal follow-up study, we aim to determine the
excess number of detected and surgically resected high-grade premalignant
lesions and early stage pancreatic cancers resulting from yearly testing using
EUS in a cohort of high-risk individuals compared to the natural disease
development and manifestation.
Study design
Multicenter prospective study
Surveillance entails an endoscopic ultrasonography. At baseline also a magnetic
resonance imaging will take place. The frequency of screening is dependent of
the findings of both screening tests and the consensus agreement of the
expert-panel. The frequency will be (1) annually in case of normal findings or
small cystic lesions, (2) after 6 months in case of the detection of a cyst
with a diameter ranging from 10 to 30 mm without the presence of malignant
features or (3) after 3 months in case of the detection of a lesion of unknown
clinical significance. Whenever a lesion is detected with a high suspicious of
being either a malignant or high-grade premalignant lesion, the lesion will be
surgically resected.
Study burden and risks
Burden: (1) yearly screening investigations (EUS (+ at baseline MRI)), (2)
yearly blood sampling and collection of feces and saliva. Risk: (1)
complications directly related to the screening procedure (EUS/MRI), (2)
screening related drawbacks being over-diagnoses, false positive test results,
and false negative test results Benefits: (1) early disease detection and
thereby reduction of pancreatic cancer related mortality, gains in life years
and preventing people from dying of pancreatic cancer. Group-relatedness: not
applicable.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
Eligible are individuals who, after evaluation by a clinical geneticist, have
an estimated >10-fold increased risk of developing pancreatic cancer, this
includes:
(1) Carriers of CDKN2A gene mutations (excl. mutation in exon 1b), regardless
of the family history of pancreatic cancer
(2) Peutz-Jeghers Syndrome patients (diagnosis based on a proven LKB1 gene
mutation and/or clinical diagnosis), regardless of the family history of
pancreatic cancer
(3) Carriers of gene mutations in BRCA1, BRCA2, PALB2, ATM, p53, or Mismatch
Repair Gene with a family history of pancreatic cancer in at least 2 family
members (at least 1 PA proven, and at least 1 also a mutation carrier)
Exclusion criteria
1) Personal history of pancreatic cancer
(2) Age younger than 18 years
(3) Individuals unable to provide informed consent either due to mental
retardation or language barrier
(4) Severe medical illness: WHO 1 to 5
(5) PRSS1 gene mutation carrier
(6) Contra-indication for EUS, due to anatomic abnormalities/surgery or
patients whish.
Individuals who already participate in the study with MRI-only (no EUS) will be
excluded if they
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL40489.078.13 |