The purpose of this study is to provide access to 18F-6-L fluorodihydroxyphenylalanine
(18F-FDOPA) positron emission tomography and computed tomography (PET/CT) imaging to patients
with neuroendocrine tumours (NET) and to collect additional data about the effectiveness of
18F-DOPA PET/CT in this patient population.
1. The overall accuracy of 18F-FDOPA PET/CT is superior to conventional imaging techniques
for the detection of neuroendocrine tumours.
2. The sensitivity of 18F-FDOPA PET/CT is superior to conventional imaging techniques for
the detection of neuroendocrine tumours.
Treatment of NET's depends on the extent of disease and rate of tumour progression. Accurate
staging is critical to establish the prognosis of the disease, to guide potentially curative
surgical approaches and to assist in therapeutic decision making between surgery,
embolization techniques and systemic therapy. Standard radiologic and nuclear medicine
techniques all have significant limitations in terms of their ability to detect these lesions
and to evaluate response to treatment. The widely used PET tracer 18F-Fluorodeoxyglucose
(18-FDG) is of limited value in NET's due to its non-specific uptake and the relatively low
mitotic rate often seen in these tumours.
Combined PET/CTutilizing 18F-FDOPA has been investigated as a potentially sensitive and
specific staging and localization technique for NETs. Expression of tumour-specific
catecholamine transport and storage mechanisms by NET cells is the basis of 18F-DOPA PET
imaging. Cellular uptake and radiopharmaceutical concentration in intracellular storage
granules within tumour cells of neuroendocrine origin and differentiation, combined with the
high sensitivity, resolution and accurate anatomic localization of PET/CT imaging, makes
18F-DOPA PET/CT potentially superior to standard nuclear medicine and radiologic techniques
for the detection and localization of functioning and non-functioning NETs. This imaging
technique not only provides specific functional and biochemical information via PET images,
but also morphological and anatomical detail via CT images leading to more accurate
localization and characterization on individual lesions. This may allow better treatment
planning as well as restaging during and after therapy to assess disease response. The
information retrieved from the hybrid 18F-FDOPA PET/CT could have a profound influence on
diagnosis and treatment of patients with NETs.
This will be an expanded access study in which adult and pediatric subjects will be invited
to participate. All subjects are informed of anticipated effects (none) and purpose of the
injected substance. Subjects are approached by their treating physicians with respect to
their willingness to participate in the proposed study based on clinical criteria. They will
then undergo a brief clinical assessment followed by the PET/CT scanning protocol.
The BC Cancer Agency anticipates a start date in August 2012 and a potential completion date
August of 2017. Three full years of data collection will provide meaningful numbers for
analysis. A total of 300 patients, including adults and pediatric patients, will be recruited
for the study. This number is based on the anticipated number of PET scan referrals expected
over a five-year study timeframe.
The primary outcomes will be estimates of sensitivity, specificity and accuracy of 18F-DOPA
PET. 95% confidence intervals will be calculated for all estimates. Outcomes will be
estimated for the whole study population and for different types of cancer.
Sensitivity (ratio of true positive lesions to total positive lesions), specificity (ratio of
true negative lesions to total negative lesions) and accuracy (ratio of total correct studies
to the total number of biopsied lesions) of 18F-FDOPA PET studies performed by the BCCA will
be obtained by comparing results of the PET scan with the gold-standard of histopathological
diagnosis when those results are available (as determined by clinical indication and
feasibility by the treating physician) and results of conventional imaging. Biopsy of lesions
is not mandated by this study. Confidence intervals (95% CI) for sensitivity, specificity and
accuracy will be calculated using exact binomial distribution.
Results will be compared to figures in the published literature. All analyses will be
performed in direct consultation with a statistician who is a member of the BC Cancer Agency